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Neuroprotection - Methods, Drugs, Markets and Companies

  • ID: 4748149
  • Report
  • June 2021
  • Region: Global
  • 844 Pages
  • Jain PharmaBiotech

This report describes the role of neuroprotection in acute disorders such as stroke and injuries of the nervous system as well as in chronic diseases such as neurodegenerative disorders because many of the underlying mechanisms of damage to neural tissues are similar in all these conditions and several products are used in more than one disorder. Over 500 products have been investigated for neuroprotective effects including those from the categories of free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators, and gene therapy. Some of the agents are old established pharmaceuticals whereas others are new biotechnology products.

Pathomechanisms of diseases are described with steps at which neuroprotective therapies are directed. Diseases covered include cerebrovascular disorders, traumatic brain injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy and ischemic optic neuropathy as well as retinal degeneration. Although anesthetics such as propofol are neuroprotective as well, neuroprotection during surgery and anesthesia is discussed with the aim of preventing and treating complications that result in CNS damage.

The report contains profiles of 141 companies that have neuroprotective products or products along with 126 collaborations. Some of the products in development at academic institutions that do not have a commercial sponsor are also included. Although an up-to-date search of the literature was performed and selected 1,100 references are included. Clinical trials of various neuroprotective agents are described and failures of trials are analyzed with suggestions for improving the selection of drugs and design of trials. The report is supplemented with 85 tables and 27 figures.

Market analysis of currently used products that have a neuroprotective effect is analyzed for the year 2020. Some of these products are approved for other indications but are known to have a neuroprotective effect. With the approval of new products and the takeover of markets for obsolete symptomatic therapies, the neuroprotection market value will rise by the year 2025 when it will constitute a major and important component of the CNS market. Forecasts are made until 2030. By that time neuroprotection will be an established part of the neurological practice and measures will be available to achieve this effect.

The report contains information on the following:

  • Introduction
  • Neuroprotective Agents
  • Neuroprotection in Cerebrovascular Disease
  • Neuroprotection in Traumatic Brain Injury
  • Neuroprotection in Spinal Cord Injury
  • Neuroprotection for Neurodegenerative Disorders
  • Neuroprotection in Parkinson Disease
  • Neuroprotection in Alzheimer Disease
  • Neuroprotection in Huntington Disease
  • Neuroprotection in Amyotrophic Lateral Sclerosis
  • Neuroprotection in Miscellaneous Neurological Disorders
  • Neuroprotection in Disorders of the Optic nerve and the Retina
  • Neuroprotection during Anesthesia and Surgery
  • Markets for Neuroprotective Therapy
  • Companies Involved in Developing Neuroprotective Therapies
Note: Product cover images may vary from those shown

Part I: Methods and Drugs

Executive Summary

1. Introduction

  • Definitions
  • Historical development of neuroprotection
  • Neurophysiological basis of neuroprotection
  • Astrocytic glycogen-derived lactate as fuel for the brain
  • Gene expression in the human brain
  • Role of astrocytes in neuroprotection
  • Role of glymphatic system in neuroprotection
  • Role of sleep in neuroprotection
  • Role of cerebral metabolism in neuroprotection
  • Role of circadian genes in neuroprotection
  • Role of blood-brain barrier in neuroprotection
  • Role of the gut microbiota in development of integrity of the BBB
  • Intrinsic neuroprotective factors
  • Neuroprotective gene expression
  • Upregulation of GADD34
  • Induction of NR4A proteins by CREB in neurons
  • Elevation PGC-1α for neuroprotection in PD
  • Neurotrophic factors
  • Intrinsic nonenzymatic antioxidants
  • Activation of transcription factor Nrf2
  • Intrinsic neuroprotective factors
  • αB-crystallin
  • Docosahexaenoic acid
  • Excitatory amino acid transporters
  • Extracellular serine protease thrombin
  • Galanin
  • Heat-shock proteins
  • Neuroglobin
  • Nuclear factor I-A
  • Prion protein
  • Rai adaptor protein
  • Stem cell factor
  • Role of the immune system in neuroprotection
  • Induction of DNA repair enzymes for neuroprotection
  • Microtubule-based neuroprotective response to axonal injury
  • Pathomechanisms of CNS injury as basis for neuroprotection
  • Biomarkers of neurological disorders and neuroprotection
  • CNS biomarker identification using proteomics
  • Brain imaging for detection of biomarkers
  • Neuroprotection in cerebral hypoxia
  • Effects of hypoxia on the brain
  • Cerebral Metabolism During Hypoxia
  • Adaptive mechanisms in hypoxia
  • Neuroprotection in hypoxia-ischemia
  • Neuroprotection in neuroinflammation
  • Pathomechanism of neuroinflammation
  • Role of microglia in neuroinflammation
  • Role of other players in neuroinflammation
  • Causes of neuroinflammation
  • Biomarkers of neuroinflammation
  • Brain imaging biomarkers of neuroinflammation
  • Neuroprotection in mental stress
  • Neuroprotection in disruption of circadian rhythms
  • Role of neuroprotection in various neurological disorders
  • Neuroprotection and neuroregeneration
  • Acute versus chronic neuroprotection
  • Discovery and evaluation of neuroprotective agents
  • Neuroprotective drug discovery
  • Discovery of CNS drugs that penetrate the blood-brain barrier
  • In vitro assays for the evaluation of neuroprotective agents
  • Oxidative injury model to test neuroprotective drugs
  • Apoptosis model for designing neuroprotective drugs
  • Transgenic mouse models of neurological disorders
  • Evaluating effects of neuroprotective drugs on living brain slices
  • Role of brain imaging in neuroprotective drug discovery and development
  • Positron emission tomography
  • Role of single photon emission computed tomography
  • Functional CT scanning to evaluate cerebrovascular protection
  • Magnetic resonance imaging for the evaluation of neuroprotectives
  • Application of nanotechnology to neuroprotection
  • Anthocyanin-loaded PEG-gold nanoparticles
  • Buckminsterfullerene C60 derivatives
  • Cadmium telluride nanoparticles prevent Aβ fibril formation
  • Ceria nanoparticles as antioxidants
  • Chitosan nanoparticles against oxidative stress
  • Nanoparticles as carriers of neuroprotective agents into the brain
  • Polymer nanoparticles
  • Squalenoyl adenosine nanoparticles
  • Evaluation criteria for potential neuroprotective agents

2. Neuroprotective Agents

  • Classification of neuroprotective agents
  • α2 adrenoreceptor agonists
  • Dexmedetomidine
  • Activated protein C
  • Activity-dependent neuroprotective protein
  • Davunetide
  • Adenosine analogs
  • Propentofylline
  • Antidepressants
  • Antidepressant-induced neurogenesis
  • Neurogenesis induced by electroconvulsive therapy
  • Neuroprotective effect of selective serotonin reuptake inhibitors
  • Fluoxetine as a neuroprotective agent
  • Antiepileptic drugs as neuroprotectives
  • BIS-001
  • Levetiracetam
  • Phenytoin
  • Valproic acid
  • Anti-neuroinflammatory agents
  • Aspirin
  • Interleukin-1 antagonists
  • COX-2 inhibitors
  • Nimesulide
  • Gold microparticles as anti-neuroinflammatory agents
  • Matrix metalloproteinase inhibitors as anti-neuroinflammatory agents
  • Minocycline
  • Prostaglandin receptor antagonists
  • Anti-apoptosis agents
  • Activated protein C
  • Calpain inhibitors
  • Caspase inhibitors
  • DNA binding drugs
  • Lithium
  • Melatonin
  • Olesoxime
  • Omega-3 fatty acids
  • Docosahexaenoic acid
  • Poly(ADP-ribose) polymerase inhibitors
  • Prevention of apoptosis by binding of proNGF to sortilin
  • Antioxidants/free radical scavengers
  • Free radical generation
  • Natural defenses against oxidative stress
  • Effects of oxidative damage
  • Oxidative damage and aging
  • Neuronal damage by free radicals
  • Oxidative damage and neurodegenerative disorders
  • Measures to control oxidative stress
  • Categories of therapeutic antioxidants
  • Alpha-phenyl-tert-butylnitrone
  • Coenzyme Q10
  • Dihydroergocryptine
  • Flavonoids
  • Mitochondria-targeted antioxidants
  • Neuroleptics as antioxidants
  • Nitrones
  • NRF2 for augmenting neuroprotection againt oxidative stress
  • Nrf2/ARE-mediated antioxidant actions of pro-electrophilic drugs
  • Quercetin
  • Translation of antioxidant neuroprotection from preclinical to clinical
  • Arimoclomol
  • Carbon monoxide and heme oxygenase
  • Cell transplants
  • Cells secreting neuroprotective substances
  • Stem cells
  • Stem cell activation for neuroprotection/regeneration by glucocorticoids
  • Use of neural stem cells to construct the blood brain barrier
  • Cytokines
  • Erythropoietin
  • Non-erythropoietic EPO variants and mimics
  • Granulocyte colony-stimulating factor
  • Delta-opioid receptor agonists
  • Delta opioid peptide-induced hibernation for neuroprotection
  • FK960
  • Gene therapy
  • Glucagon-like peptide
  • Glatiramer acetate
  • Glutamate antagonists
  • Neuroprotection by scavenging blood glutamate
  • Glutamate transporters
  • Glutamate transporter-mediated neuroprotective effect of drugs
  • Neuroprotection by targeting KAI subunit of kainate receptor
  • Glycine-proline-glutamate analogs
  • Hydrogen sulfide
  • Hibernation induced by hydrogen sulfide
  • NMDA receptor ion channel complex
  • NMDA receptor antagonists
  • NMDA NR2B subunit receptor antagonists
  • Ifenprodil
  • Memantine as a neuroprotective agent
  • NAALADase inhibitors
  • Gacyclidine
  • N-alkylglycines
  • AMPA receptor modulators
  • Metabotropic glutamate receptor modulators
  • Cannabinoids
  • Dexanabinol
  • Glutathione
  • Heat shock proteins
  • Histone deacetylase inhibitors for neuroprotection
  • Hormones
  • Estrogen and neuroprotection
  • Neuroprotective effect of estrogen receptor ligands
  • Selective estrogen receptor modulators
  • Mitochondrial mechanisms of estrogen neuroprotection
  • Insulin
  • Ion Channel modulators
  • Calcium channel blockers.
  • Ziconotide
  • Na + channel blockers.
  • Neuroprotective potassium channel inhibitors
  • Kynurenine inhibitors
  • Leukocyte adhesion inhibitors
  • Modafinil
  • Neurite outgrowth-promoting agents
  • Monoclonal antibodies
  • Neuroimmunophilins
  • Cyclosporin-A
  • FK506
  • Rapamycin
  • Neurotrophic factors
  • Activity-dependent neurotrophic factor
  • Bone morphogenetic proteins
  • Brain-derived neurotrophic factor
  • Ciliary neurotrophic factor
  • Fibroblast growth factors
  • Glial cell line-derived neurotrophic factor
  • Insulin-like growth factor
  • Nerve growth factor
  • Neurotrophins
  • Osteogenic protein-1
  • Pigment epithelium-derived factor
  • Transforming growth factor-1
  • Vascular endothelial growth factor
  • Neurotrophic factor-related neuroprotective agents
  • Amitriptyline as a TrkA and TrkB receptor agonist
  • Colivelin
  • Gambogic amide
  • Inosine
  • Meteorin
  • Oxygen-regulated protein 150 kD
  • Prosaptide
  • Siagoside
  • Small molecule activators of the Trk receptors
  • Nicotine and nicotinic receptor agonists
  • Neuroprotective effect of galantamine mediated via α7nAChRs
  • Galantamine-induced Aβ clearance via α7nAChRs
  • Nitric oxide-based neuroprotection
  • Nitric oxide synthase inhibitors
  • Nitric oxide mimetics
  • Nitric oxide donating derivatives
  • Nootropics
  • Piracetam
  • Nutraceuticals and naturally-derived compounds
  • Cinnamon
  • Coffee
  • Creatine
  • Curcumin/curry
  • Mechanism of neuroprotective effect of curcumin
  • Flavonoids
  • Glyceryltriacetate
  • Green tea
  • Herbal preparations
  • Flavonoid wogonin
  • Ginseng
  • Nicotinamide
  • Punicalagin from pomegranate
  • Resveratrol
  • Osmotic diuretics
  • Mannitol
  • Osteopontin
  • Oxygen therapeutics
  • Oxygen carriers
  • Hemoglobin-based oxygen carriers
  • Perfluorocarbons as oxygen carriers
  • Hyperbaric oxygen therapy
  • P7C3 compounds
  • Peptides
  • C3-derived peptide for neuroprotection and neuroregeneration
  • Corticotropin-releasing hormone
  • Thyrotropin-releasing hormone
  • Vasoactive intestinal peptide
  • Pharmacological preconditioning
  • PPARs as drug targets for neuroprotection
  • Proteins
  • Amyloid precursor protein
  • Protein kinase C activators
  • PSD-5 antagonists
  • Riluzole
  • Role of RNA interference in neuroprotection
  • Role of miRNA in neuroprotection
  • Sigma receptor agonists as neuroprotective agents
  • SIRT group of proteins
  • Statins
  • Steroids
  • Dehydroepiandrosterone
  • Sulforaphane
  • Tauroursodeoxycholic acid
  • Tetanus toxin as a neuroprotective agent
  • Thrombolytic agents as neuroprotective agents
  • Uncoupling protein 2
  • Vaccines as neuroprotectives
  • Vitamins as neuroprotective agents
  • Vitamin B12
  • Vitamin D
  • Unconventional biologicals
  • Non-pharmacological approaches to neuroprotection
  • Caloric restriction
  • Cerebral exercise
  • Bilingualism for prevention of decline of mental function
  • Electrical fields for improvement of cerebral function in neurodegeneration
  • Environmental enrichment
  • Hypothermia
  • Limitations of hypothermia
  • Hypothermic neuroprotection in hypoxia-ischemia
  • Ketogenic diet
  • Mediterranean diet
  • Nonpharmacological preconditioning for neuroprotection
  • Physical exercise
  • Suspended animation and neuroprotection
  • Transcranial magnetic stimulation

3. Neuroprotection in Cerebrovascular Disease

  • Introduction
  • Pathophysiology of cerebral ischemia
  • Calcium overload
  • Cerebral edema in stroke
  • Cytokines and adhesion molecules in stroke
  • Adhesion molecules
  • Interleukin-1 and IL-6
  • Tumor necrosis factor-α
  • DNA damage and repair in cerebral ischemia
  • Gene expression in response to cerebral ischemia
  • Glutamate as a biomarker of stroke
  • Heat shock proteins in stroke
  • Ion channel dysfunction in stroke
  • Neuroinflammation in cerebral infarction
  • Neurotrophic factors in stroke
  • Problems requiring investigation of the role of NTFs in stroke
  • Neurovascular dissociations after ministrokes
  • Nitric oxide in cerebral ischemia
  • Oxygen free radicals in cerebral ischemia
  • Poly(ADP-ribose) polymerase (PARP) gene
  • Protease-activated receptor 1
  • Effect on the brain of cessation of cerebral circulation
  • Reperfusion injury after cerebral ischemia
  • Neuroprotection according to zones in cerebral infarction
  • Zone of ischemic infarction
  • Penumbra
  • Current management of stroke
  • Neuroprotection in stenosis of intracranial arteries
  • Neuroprotection in stroke with intracerebral hemorrhage
  • Neuroprotection in cerebrovascular malformations
  • Arteriovenous malformations
  • Cavernous cerebrovascular malformations
  • Neuroprotective strategies for ischemic stroke in patients with dementia
  • Neuroprotection in transient ischemic attacks
  • Secondary prevention of stroke
  • Neuroprotective therapies for stroke
  • Neuroprotective strategies according to pathomechanism of stroke
  • Pharmacologic neuroprotective agents for stroke
  • αB-crystallin as a neuroprotectant in stroke
  • Acid-sensing ion channel blockers
  • Adrenergic receptor antagonists
  • AMPA receptor antagonists as neuroprotectives for stroke
  • Anesthetic agents as neuroprotectives in stroke
  • Propofol as neuroprotective in stroke
  • Antiapoptotic neuroprotectives
  • NIM811
  • Creatine as neuroprotective in stroke
  • Lithium as a neuroprotective in stroke
  • TUDCA as a neuroprotective in stroke
  • Antidepressants as neuroprotectives agents in stroke
  • Fluoxetine as neuroprotectectant in stroke
  • Antiepileptic drugs as neuroprotectives in stroke
  • Tiagabine
  • Topiramate
  • Anti-HMGB1 monoclonal antibody
  • Antiinflammatory agents
  • Cox-2 inhibitors for ischemic stroke
  • Minocycline for neuroprotection in stroke
  • Antioxidant approaches
  • Carnosine as a neuroprotective in stroke
  • Dehydroascorbic acid
  • Tocotrienols
  • Uric acid
  • Arimoclomol for stroke
  • Cardiac glycosides as neuroprotectives in stroke
  • Clenbuterol
  • Coagulation inhibitors as neuroprotectives
  • Heparin and enoxaparin
  • Warfarin vs dabigatran
  • Apixaban
  • Curcumin as a neuroprotectant in stroke
  • Docosahexaenoic acid for ischemic stroke
  • Ephrin-A5 blockers
  • Estrogen for stroke
  • Extendin-4
  • Flavones for neuroprotection in stroke
  • Epicatechin
  • Isorhamnetin
  • Glutamate clearance from blood
  • Hamartin induction by cerebral ischemia as a basis for neuroprotection
  • Histone deacetylase inhibitors for neuroprotection in stroke
  • Histamine H2-receptor modulation
  • Inosine for stroke
  • Insulin-like growth factor-I
  • Intravenous immunoglobulin as neuroprotective in stroke
  • Ischemic preconditioning for neuroprotection in stroke
  • Ketone bodies for neuroprotection in stroke
  • Magnesium
  • Mineralocorticoid receptor blockade for neuroprotection
  • miR-223 and neuroprotection in stroke
  • NA-1 as neuroprotective against ischemic stroke
  • Nasal delivery of neuroprotective agents in stroke
  • Nerinetide
  • Neuroserpin as a neuroprotective in stroke
  • N-2-mercaptopropionyl glycine
  • NeuroAiD
  • Neurotrophic factors as neuroprotectives for stroke
  • Brain-derived neurotrophic factor
  • Cerebral dopamine neurotrophic factor
  • Fibroblast growth factor
  • Granulocyte colony stimulating factor
  • Granulocyte-macrophage colony-stimulating factor
  • Glial cell line-derived neurotrophic factor
  • Insulin-like growth factor-1
  • Neuregulin-1
  • VEGFD delivered intranasally
  • NO-based strategies for neuroprotection in cerebral ischemia
  • NOX-4 inhibitors for neuroprotection in stroke
  • Omega-3 fatty acids for neuroprotection after cerebral ischemia-hypoxia
  • Pannexin channel blockers for neuroprotection in stroke
  • Perlecan domain V
  • Peroxisome proliferator-activated receptor- agonists
  • Pioglitazone for reduction of stroke risk
  • PGE2 EP2 receptor activation
  • Progesterone
  • Proteoglycan-degrading enzymes
  • Proteosome inhibitors
  • Statins for prevention and neuroprotection in stroke
  • Sildenafil
  • Stroke vaccine
  • Thrombosis inhibitors
  • Aspirin
  • Clopidogrel
  • Dipyridamole
  • Ticagrelor
  • Tissue plasminogen activator as neurorestorative in cstroke
  • Vitamin E for neuroprotection in stroke
  • Neuroprotection in ischemia-reperfusion injury
  • Aminoguanidine
  • Dexmedetomidine
  • Methylene blue for neuroprotection in ischemia-reperfusion injury
  • Miscellaneous agents for neuroprotection in reperfusion injury
  • Neuroprotection by treatment of cerebrovascular malformations
  • Arteriovenous malformations
  • Cerebral cavernous malformations
  • Prevention of hemorrhage following ischemic stroke
  • Non-pharmacological neuroprotective therapies for stroke
  • Blood replacement for neuroprotection after cerebral ishemia in mice
  • Hypothermia for neuroprotection in acute stroke
  • Hyperbaric oxygen therapy for neuroprotection in acute stroke
  • Hypothermia combination with other neuroprotective strategies
  • Infrared laser therapy for ischemic stroke
  • Preconditioning for neuroprotection against cerebral ischemia
  • Neuroprotection in ischemia/reperfusion injury
  • Neurosurgical procedures for stroke
  • Neurosurgical procedures for neuroprotection in acute stroke
  • Decompressive hemicraniectomy
  • Thrombectomy
  • Stenting
  • Multiple endovascular modalities
  • Neurosurgical procedures for chronic cerebral ischemia
  • Neurostimulation of sphenopalatine ganglion
  • Stent versus surgery for asymptomatic carotid stenosis
  • Neurorehabilitation in relation to neuroprotection in stroke
  • Protective effect of physical activity on stroke in the elderly
  • Biological therapies for stroke
  • Cell therapy for stroke
  • Stem cell transplant for stroke
  • Preconditioning with hyperbaric oxygen for stem cell therapy
  • Immortalized cell grafts for stroke
  • Stimulation of instrinsic stem cells for repair of brain in stroke
  • Gene therapy for neuroprotection in cerebrovascular disease
  • Regulation of microRNAs for neuroprotection in cerebral ischemia
  • RNAi-based therapy for neuroprotection in stroke
  • Vaccines for neuroprotection in stroke
  • Neuroprotective therapies for cerebral ischemia: clinical trials
  • Albumin
  • Free radical scavengers
  • DP-b99
  • Mildronate
  • Perindopril
  • Failed clinical trials of neuroprotection in stroke
  • Ancrod
  • Aptiganel
  • Cerovive
  • Citicoline
  • Desmoteplase
  • Erythropoietin as a neuroprotective in stroke
  • Selfotel
  • Lubeluzole
  • Nalmefene
  • Gavestinel
  • Nimodipine
  • Sipatrigine
  • Causes of failure of stroke trials
  • Measures for prevention of failures in stroke trials
  • Design of acute stroke trial to facilitate drug approval
  • The ideal neuroprotective agent for stroke
  • Prevention of stroke
  • Concluding remarks and future of neuroprotection in stroke

4. Neuroprotection in Traumatic Brain Injury

  • Introduction
  • Cerebral hypoxia/ischemia as a complication of trauma
  • Epidemiology of TBI
  • TBI in the military
  • Pathophysiology of TBI
  • Immediate damage following TBI
  • Blast injury sequelae
  • Cerebral edema following TBI
  • Neurometabolic cascade after TBI
  • Delayed damage following TBI
  • Mechanism of axonal damage after TBI
  • Role of neuroinflammation in TBI
  • BBB damage after TBI
  • Molecular events following TBI
  • Chronic traumatic encephalopathy
  • Neurocognitive sequelae of TBI
  • Changes in neurotrophic factors following TBI
  • Changes in neurotransmitters following TBI
  • Proteomics of TBI
  • Genetic influences on outcome following TBI
  • Management of TBI
  • Management during acute phase of head injury
  • Control of cerebral edema and intracranial pressure
  • Corticosteroids
  • Decompressive craniectomy
  • Personalized approach to cerebral edema in TBI
  • Neuroprotection in TBI
  • Amantadine
  • Antioxidants
  • Barbiturates
  • β- and γ-secretase inhibitors
  • Beta blockers
  • Bradykinin B2 antagonists
  • Cell cycle inhibitors for TBI
  • COX-2 inhibitors for neuroprotection in TBI
  • Cyclosporin for neuroprotection in TBI
  • Dexanabinol for TBI
  • Erythropoietin for neuroprotection in TBI
  • Gold implants for neuroprotection in focal TBI
  • Histone deacetylase inhibitors for neuroprotection in TBI
  • Inhibitors of integrated stress response
  • Levosimendan
  • Magnesium sulfate
  • Minocycline for TBI
  • Multipotential neuroprotective agents for TBI
  • Neurotrophic factors for TBI
  • Neurosteroids as neuroprotective agents for TBI
  • NMDA receptor antagonists
  • Neuroprotection in TBI against glutamate-induced excitotoxicity
  • NP-1
  • Nogo-A inhibitor
  • Nutritional approaches to neuroprotection in TBI
  • Branched chain amino acids to ameliorate cognitive impairment in TBI
  • Creatine for neuroprotection in TBI
  • Nicotinamide for neuroprotection in TBI
  • Omega 3 fatty acids as neuroprotectives in TBI
  • Oxygen carriers for TBI
  • Polyethylene glycol for neuroprotection in TBI
  • Propofol for neuroprotection in TBI
  • Rapamycin as neuroprotective in TBI
  • Simvastatin as neuroprotective in TBI
  • Statins as neuroprotective agents in concussion
  • Targeting mitochondrial pathology in TBI
  • Thyrotropin-releasing hormone analogs
  • Tissue plasminogen activator
  • Biological approaches to neuroprotection in TBI
  • Antisense approaches to TBI
  • Cell therapy for TBI
  • Limitations of stem cell therapy for acute TBI
  • Stem cell-derived exosomes for treatment of TBI
  • Gene therapy for TBI
  • Vaccines for TBI
  • Non-pharmaceutical approaches to neuroprotection in TBI
  • Deep brain stimulation for TBI
  • Hyperbaric oxygen therapy for TBI
  • Hypothermia
  • Reduction of microglial migration after TBI
  • Vacuum for mechanical tissue resuscitation in TBI
  • Prophylactic neuroprotection against TBI
  • Role of helmets in protection against TBI
  • Role of physical exercise in protection against TBI
  • Neuroprotection against late sequelae of TBI
  • Antiepileptic drugs for prevention of seizures and neuroprotection
  • Neuroprotection during rehabilitation phase of TBI
  • Neuroregeneration following TBI
  • Intrinsic factors that influence regeneration following TBI
  • Causes of lack of regeneration following TBI
  • Approaches to regeneration of the brain following TBI
  • Clinical trials of neuroprotective agents in TBI
  • Ongoing clinical trials in TBI
  • Failed clinical trials in TBI
  • Differences between clinical trials and studies in animal models of TBI
  • Subgroup analysis
  • Improving the clinical trial design
  • Clinical trials combining multiple treatment strategies
  • Shortening the trial time
  • Conclusions and future of neuroprotection in TBI

5. Neuroprotection in Spinal Cord Injury

  • Introduction
  • Pathophysiology of SCI
  • Secondary mechanisms of SCI
  • Neurotrophic factor changes in SCI
  • Management of SCI
  • Pharmacological neuroprotective agents for SCI
  • 4-aminopyridine
  • Antibodies as neurite growth inhibitors in SCI
  • Antiexcitotoxic agents
  • Gacyclidine
  • GM-1 ganglioside
  • Bacterial enzyme chondroitinase ABC
  • Docosahexaenoic acid as neuroprotective in SCI
  • Erythropoietin as a neuroprotective in SCI
  • Free radical scavengers for neuroprotection in SCI
  • Immunosuppressants as neuroprotectants in SCI
  • Interleukin-10 for neuroprotection in SCI
  • Matrix metalloproteinase inhibitors for SCI
  • Methylprednisolone
  • Minocycline as neuroprotective in SCI
  • Modulation of macrophage responses for neuroprotection after SCI
  • Neurotrophic factors for neuroprotection after SCI
  • Fibroblast growth factors in the management of SCI
  • Promotion of regeneration of neurons in SCI
  • Rho pathway and Rho antagonists in SCI
  • Riluzole and methylprednisone as neuroprotectants in SCI
  • Selenium as a neuroprotective for SCI
  • Sialidase for enhancing recovery after SCI
  • Targeting the inflammatory response for neuroprotection in SCI
  • Uric acid as neuroprotective in SCI
  • Non-pharmacological approaches to SCI
  • Hyperbaric oxygen therapy
  • Hypothermia for SCI
  • Cell therapy for SCI
  • Fetal neural grafts for SCI
  • Olfactory-ensheathing cells for SCI
  • Oligodendrocyte precursor cells for treatment of SCI
  • Schwann cell transplants for SCI
  • Transplantation of glial cells for SCI
  • Stem cells for SCI
  • Bone marrow stem cells for SCI
  • Transplantation of ESCs for SCI
  • Transplantation of induced pluripotent stem cells in SCI
  • Transplantation of MSCs for SCI
  • Transplantation of NSCs for SCI
  • Transdifferentiation of stem cells into cholinergic neurons for SCI
  • Gene therapy for SCI
  • Combined approaches to spinal cord injury
  • Discovery of new targets for neuroprotective therapies in SCI
  • Clinical trials in SCI
  • Concluding remarks

6. Neuroprotection in Neurodegenerative Disorders

  • Introduction
  • Pathomechanism of neurodegeneration
  • Aging and neurodegeneration
  • α-synuclein in neurodegeneration and neuroprotection
  • Dysregulation of cyclin-dependent kinase 5
  • Dysregulation of translation
  • Exosomes in CNS neurodegeneration and neuroregeneration
  • Genomics of neurodegenerative diseases
  • Impairment of neural transport in neurodegenerative disorders
  • Lack of neurotrophic factors
  • Mitochondrial damage leading to apoptosis
  • Neuroinflammation in neurodegenerative disorders
  • Neurodegeneration associated with chronic repeated cerebral injuries
  • Neurodegeneration associated with protein misfolding
  • Modulation of neurodegeneration by molecular chaperones
  • Intrabodies targeting protein misfolding in neurodegeneration
  • Targeting proteins aggregation to prevent amyloid formation
  • Tau and neurodegeneration
  • Role of apoptosis in neurodegenerative disorders
  • Role of glia in neurodegeneration
  • Role of metals in neurodegeneration
  • Spread of neurodegeneration
  • TDP-43 proteinopathy and neurodegenerative diseases
  • Viral infections and neurodegeneration
  • AIDS and the nervous system
  • Avian influenza as cause of neurodegeneration
  • Neurodegenerative disorders with dementia
  • Dementia with Lewy bodies
  • Frontotemporal dementia
  • Progressive supranuclear palsy
  • Genetic disorders with neurodegeneration
  • Batten disease
  • Cell and gene therapies
  • Cerliponase alfa
  • Familial dysautonomia
  • Friedrich ataxia
  • Pathomechanism of FA
  • Neuroprotection in FA
  • Leigh syndrome
  • Niemann-Pick type C disease
  • Spinal and bulbar muscular atrophy
  • Spinal muscular atrophy
  • Creutzfeldt-Jakob disease
  • Neuroprotection in Creutzfeldt-Jakob disease
  • Pharmacological neuroprotectants against CJD
  • Innovative approaches to neuroprotection in CJD and future prospects
  • Approaches to neuroprotection in neurodegenerative disorders
  • Glutamate-based therapies for neurodegenerative disorders
  • Histone deacetylase inhibitors for neurodegenerative disorders
  • Intermittent fasting for neuroprotection
  • Iron chelation for neuroprotection
  • Mitochondria permeability transition pore complex and neuroprotection
  • Modulation of proteostasis in neurodegenerative disorders
  • Targets to limit protein aggregation in neurodegenerative diseases

7. Neuroprotection in Parkinson Disease

  • Introduction
  • Epidemiology of Parkinson's disease
  • Pathophysiology of Parkinson's disease
  • Alteration of dopamine homeostasis
  • Apoptosis
  • Calcium interaction with α-synuclein
  • Disruption of iron homeostasis
  • Excitotoxicity
  • Genes and PD
  • Histone deacetylase 4 as a regulator of progression of PD
  • Oxidative stress
  • Propagation of pathologic α-synuclein from the gut to the brain in PD
  • Role of neurotrophic factors
  • Role of misfolding proteins
  • Role of a-synuclein in dementia of PD
  • Synaptic vesicle glycoprotein 2C disruption in PD
  • Neuroprotective strategies for PD based on pathomechanism
  • A genetic animal model of PD for testing neuroprotective strategies
  • Aldehyde dehydrogenase 1 protects nigrostriatal dopaminergic neurons
  • RNAi screening to identify neuroprotective genes in a PD model
  • Strategies to stop aggregation of a-synuclein
  • Targeting mitochondrial dysfunction in PD
  • Management of Parkinson's disease
  • Limitation of conventionally administered dopamine therapy
  • Neuroprotective therapy in PD
  • Neuroprotective effect of currently used drugs for PD
  • Pramipexole
  • Rasagiline mesylate
  • Ropinirole
  • Rivastigmine for treatment of dementia and falls associated with PD
  • Selegiline
  • Non-pharmacological strategies for neuroprotection in PD
  • Deep brain stimulation for PD
  • Effect of exercise and environmental enrichment on PD
  • Calorie restriction in PD
  • Development of neuroprotective therapies for PD
  • 2B3-201 for targeted delivery of methylprednisolone
  • 9-methyl-β-carboline
  • Adenosine AA2  receptor antagonists
  • Ambroxol
  • Antiapoptotic strategies for PD
  • ATP13A2 activation
  • Atremorine
  • Augmenting CNS glucocerebrosidase activity
  • β2-Adrenoreceptor agonists
  • BT13 as GDNF receptor agonist
  • Calcium channel blockers for PD
  • Cell therapies for PD
  • Stem cells for PD
  • Activation of endogenous stem cells and neural precursors
  • Pluripotent stem cell-derived neurons
  • Transplantation of iPSC-derived neural progenitors
  • Cogane
  • Conserved dopamine neurotrophic factor for PD
  • Doxycyline as a neuroprotectant in PD
  • Free radical scavengers for neuroprotection in Parkinson’s disease
  • Antioxidants
  • Diapocynin
  • Tea extracts as neuroprotectives
  • Gene therapy for PD
  • Implantation of genetically engineered cells
  • Gene therapy using GDNF
  • Parkin gene therapy
  • Viral vector-based ubiquitination to prevent spread of α-synuclein
  • Concluding remarks about gene therapy for PD
  • Heat shock protein 70
  • Liver X receptor β agonists
  • Melatonin as a neuroprotectant in PD
  • Nicotine as a neuroprotective in PD
  • Nilotinib for PD
  • Neuroprotective effect of leucine-rich repeat kinase-2 inhibitors
  • Neuroprotective effect of DJ-1 protein
  • Neurotrophic factors
  • Basic fibroblast growth factor for PD
  • BDNF for PD
  • GDNF for PD
  • MANF for PD
  • Neurturin for PD
  • Platelet derived growth factor
  • Nrf2-mediated neuroprotection in PD
  • Nuclear receptor-related 1:Retinoid X receptor α activation
  • Omega-3 polyunsaturated fatty acids
  • RAB3B overexpression
  • Reservatrol for PD
  • RNAi therapy for PD
  • Safinamide
  • Sirtuin 2 inhibitors for neuroprotection in PD
  • Squalamine and PD
  • Statins and PD
  • Targeting Bax
  • Vitamin D for neuroprotection in PD
  • Vaccine for PD
  • Clinical trials of neuroprotection in Parkinson's disease
  • Evaluation of neuroprotective therapies for PD
  • Current status and future challenges for neuroprotection in PD

8. Neuroprotection in Alzheimer Disease

  • Introduction
  • Pathomechanism of Alzheimer's disease
  • Pathology of AD
  • Cerebral atrophy and neuronal loss
  • Neuritic plaques and neurofibrillary tangles
  • Role of tau in the pathogenesis of AD
  • RNA-binding proteins and AD
  • Amyloid precursor protein
  • APP intracellular domain
  • Relation of APP mutations to CNS disorders
  • Relation of APP to Aβ deposits and pathogenesis of AD
  • Role of neprilysin in Aβ degradation
  • Role of secretases in amyloid cascade
  • Role of nicastrin
  • Neurotoxicity of Aβ deposits
  • Aβ production and clearance
  • Aβ-mediated synaptic and cognitive deficits
  • Interaction of Aβ with neuron-specific Na+/K+-ATPase α3 subunit
  • Relation of Aβ deposits to synaptic activity
  • Role of dsDNA breaks in neurodegeneration due to Aß
  • Sequence of events in neurotoxicity of Aβ
  • Impairment of mitochondrial energy metabolism
  • Disturbances in brain metabolism in early AD
  • Disturbance of lipid metabolism in the brain
  • Dopamine and AD
  • Functioning role of genes in pathomechanism of AD
  • Insulin, diabetes and AD
  • Mechanisms underlying cognitive deficits in AD
  • Microglia and AD
  • Neuroinflammation and AD
  • Nitric oxide and AD
  • Oxidative stress and AD
  • Spread of neurodegeneration
  • Risk factors in the etiology of AD
  • Epigenetic link between aging and AD
  • Level of education/type of job and risk of AD
  • Metals and AD
  • Psychosocial stress and risk of AD
  • Sleep deprivation
  • Traumatic brain injury and AD
  • AD and cognitive impairment with aging
  • Concluding remarks on pathophysiology of AD
  • Management of Alzheimer's disease
  • Neuroprotective approaches to Alzheimer's disease
  • Antiapoptotic agents
  • Phenserine
  • Antiinflammatory drugs for neuroinflammation
  • Etanercept
  • NSAIDS for AD
  • Nitric oxide-donating NSAIDs
  • PPARgamma agonists
  • Antioxidant and free radical scavengers
  • Colostrinin
  • Curcumin
  • Dehydroascorbic acid
  • Melatonin
  • Reservatrol for AD
  • Antisense approaches to AD
  • Antisense PNA in AD
  • Antisense tau in AD
  • Cell therapy for AD
  • Choroid plexus epithelial cells for AD
  • Stem cell transplantation for AD
  • Autologous adipose tissue derived mesenchymal stem cells
  • Neural stem cells transplantation
  • Neuronal differentiation of implanted NSCs enhanced by drugs
  • NSCs improve cognition in AD via BDNF
  • Potential benefits of grafting NSCs in AD
  • Use of autologous stem cells for dementia
  • Clearance of Aβ deposits and plaques
  • Galantamine-induced Aβ clearance
  • Monoclonal antibodies for removal of Aβ
  • Crenezumab
  • Gantenerumab
  • Solanezumab
  • Nanotechnology for removal of Aβ deposits
  • Nilotinib
  • Cholesterol lowering agents for AD
  • Statins for reducing the risk of AD
  • Gene therapy for Alzheimer disease
  • Rationale
  • NGF gene therapy for AD
  • FGF2 gene transfer in AD
  • Neprilysin gene therapy
  • Viral gene transfer of APPsα for rescuing synaptic failure in AD
  • Gene vaccination
  • Combination of gene therapy with other treatments for AD
  • Glutamate antagonists
  • Memantine
  • Inhibition of Aβ formation
  • Chelation of metals
  • Clioquinol
  • Copper chelation
  • Next generation multifunctional chelating agents for AD
  • Secretase modulators
  • Neuroprotection by α-secretase cleaved APP
  • Inhibitors of β-secretase
  • Inhibitors of γ-secretase
  • Miscellaneous neuroprotective agents
  • Cerebrolysin
  • Ginko biloba
  • Tetrahydrocannabinol for neuroprotection in AD
  • Nanobiotechnology-based therapeutics for AD
  • Nanobody-based drugs for AD
  • Nanoencapsulation for delivery of vitamin E for Alzheimer disease
  • Selegiline-PEG nanoparticles targeting Aβ fibrils in Alzheimer disease
  • Neurotrophic factors for neuroprotection in AD
  • AL-108
  • Brain derived neurotrophic factor
  • Neotrofin (AIT-082)
  • Small molecule compounds binding to neurotrophin receptor p75NTR
  • Limitations of the use of NTFs for AD
  • Neuroprotective effect drugs not primarily developed for AD
  • Antiepiletic drugs
  • Lamotrigine
  • Levetiracetam
  • Antimicrobial drugs
  • Dapsone
  • Antimicrobial drugs against Chlamydia pneumoniae
  • Antiviral therapy in AD
  • Antidiabetic drugs
  • Insulin
  • Metformin
  • Rosiglitazone
  • Antihypertensive drugs
  • Angiotensin-converting enzyme inhibitors
  • Angiotensin receptor blockers
  • Bexarotene
  • Dimebon
  • Drugs acting on estrogen receptors
  • Estrogen
  • Raloxifene
  • Granulocyte-macrophage colony-stimulating factor
  • Inhibitors of neuroinflammation
  • Ceramide
  • CSP-1103
  • Fingolimod
  • Interferon beta-1a
  • Lithium
  • MAO-B inhibitors
  • Ladostigil tartrate
  • Methylene blue
  • Phosphodiesterase inhibitors as neuroprotectives
  • Rapamycin
  • Saracatinib
  • Testosterone
  • Valproic acid
  • Restoration of factors deficient in the aging brain
  • Reversal of cognitive impairment in aging by activation of creb protein
  • Reversal of cognitive impairment in aging by GDF11 protein
  • Restoration of repressor element 1-silencing transcription factor
  • Vaccines for AD
  • Active immunization with Aβ
  • Passive immunization with MAbs
  • Other vaccines for AD
  • Mechanism of reduction of A plaque pathology by immunization
  • Perspectives on vaccines for AD
  • Vitamins
  • Vitamin E as antioxidant
  • Vitamin B for lowering homocysteine
  • Folic acid
  • Combined therapeutic approaches to AD
  • Clinical trials in AD
  • Concluding remarks on clinical trials of AD
  • Future prospects of neuroprotection in AD
  • Mild cognitive impairment
  • Relation of MCI to AD
  • Neuroprotection in MCI
  • Pharmacological approaches for MCI
  • Non-pharmacological approaches to MCI and AD

9. Neuroprotection in Huntington Disease

  • Introduction
  • Pathophysiology of HD
  • Management of Huntington's disease
  • Neuroprotection in Huntington's disease
  • Antipsychotic D2 and 5-HT1A antagonists
  • Caspase inhibitors
  • Cysteine and neuroprotection in HD
  • Cysteine metabolism reprogramming for neuroprotection in HD
  • Cysteamine
  • Drugs that block inappropriate calcium release from neurons
  • Enhancing protease activity for clearance of mHtt
  • Eicosapentaenoic acid
  • Fingolimod
  • Free radical scavengers
  • Histone deacetylase inhibitors
  • Phosphodiesterase inhibitors
  • Polyglutamine aggregation inhibitors
  • Pramipexole
  • Pridopidine
  • RRAS signaling pathway inhibition
  • Simvastatin as a neuroprotective in HD
  • Single chain Fv antibodies
  • SIRT1 activators for neuroprotection in HD
  • SIRT2 inhibitors for neuroprotection in HD
  • Synaptic activation of NMDA receptors
  • Targeting mutant huntingtin protein
  • Tetrabenazine
  • Combinatorial therapy and targeting multiple pathways in HD
  • Cell therapy for HD
  • Cell transplants for HD
  • Stem cell-based therapy for HD
  • Neurotrophic factors and gene therapy
  • Antisense therapeutics for Huntington's disease
  • HTTRx/RG6042 for HD
  • RNAi-based therapies for Huntington's disease

10. Neuroprotection in Amyotrophic Lateral Sclerosis

  • Introduction
  • Pathophysiology of ALS
  • Neuroprotective therapies for ALS
  • Activated protein C
  • AIMSPRO
  • Anakinra
  • Antisense therapy
  • Arimoclomol for ALS
  • Ceftriaxone for ALS
  • Coenzyme Q10 for ALS
  • COX-2 inhibitors for ALS
  • Dexpramipexole
  • Diallyl trisulfide
  • Edaravone for ALS
  • Erythropoietin for ALS
  • Gene therapy for ALS
  • Gene editing for ALS
  • Glatiramer acetate
  • GM604
  • Insulin-like growth factor
  • Ketogenic diet for neuroprotection in ALS
  • Lenalidomide
  • Lithium for neuroprotection in ALS
  • Masitinib
  • Melatonin for ALS
  • Methylcobalamin
  • Olesoxime as neuroprotective for ALS
  • ONO-2506
  • Riluzole
  • RNAi-based therapy for ALS
  • Sodium phenylbutyrate
  • Stem cell therapy
  • Clinical applications
  • Stem cell-based drug discovery for ALS
  • Suppressors of mTDP-43 toxicity
  • Talampanel
  • Tamoxifen
  • Vaccination for ALS caused by SOD1 mutations
  • Vascular endothelial growth factor for ALS
  • Vitamin E for ALS
  • Clinical trials  of neuroprotective therapies for ALS
  • Concluding remarks and future prospects
  • Multi-omics approach to ALS
  • Use of CRISPR/Cas9 technology to find new targets in ALS
  • Concluding remarks on neuroprotection in ALS

11. Neuroprotection in Miscellaneous Neurological Disorders

  • Introduction
  • Neuroprotection in synaptopathies
  • Neuroprotection in ASD
  • Neuroprotection in fragile X syndrome
  • Neuroprotection in dementia
  • Age-related dementia
  • Aging brain and oxidative stress
  • Hsp70 and age-related neurodegeneration
  • Pharmacological approaches for treatment of age-related dementia
  • Mental training to prevent decline of mental function with aging
  • Physical exercise to prevent decline of mental function with aging
  • Concluding remarks on neuroprotection of the aging brain
  • Vascular dementia
  • Prediction of dementia in persons with vascular risk factors
  • Management of subcortical vascular dementia
  • Neuroprotection in Lewy body dementia
  • Neuroprotection in AIDS dementia
  • Multiple system atrophy
  • Epilepsy
  • Mechanisms of neuronal damage in epilepsy
  • Strategies for neuroprotection in epilepsy
  • AEDs and neuroprotection
  • Cell therapy for neuroprotection in epilepsy
  • Cell therapy of posttraumatic epilepsy
  • Cell therapy for temporal lobe epilepsy
  • Cell therapy for pharmacoresistant epilepsies
  • Drugs targeting mossy cells in drug-resistant epilepsy
  • Gene therapy for neuroprotection in epilepsy
  • Hyaluronan-based preservation of brain ECS volume
  • Hypothermia for neuroprotection in status epilepticus
  • Ketogenic diet for prevention of seizures
  • miR-211 as an attenuator of cholinergic-mediated seizures
  • Multiple sclerosis
  • Introduction
  • Epidemiology of multiple sclerosis
  • Pathophysiology
  • Current management of multiple sclerosis
  • Specific therapies for MS based on pathomechanism
  • Neuroprotection in multiple sclerosis
  • Clinical trials of neuroprotective therapies for MS
  • Neuroprotection by control of progressive forms of multiple sclerosis
  • Neuroprotection by controlling autoimmune inflammation in the brain
  • Neuroprotection by sealing the BBB with imatinib
  • TRPM4 cation channel blockers
  • Remyelination for neuroprotection in multiple sclerosis
  • Agents for neuroprotection in multiple sclerosis
  • Angiotensin-II inhibitors
  • Antiglutamate agents
  • Antioxidants for neuroprotection in MS
  • Antisense and RNAi approaches to MS
  • B cell depletion therapy
  • Cell therapy for multiple sclerosis
  • Cannabinoids for neuroprotection in MS
  • Cladribine
  • Curcumin as a neuroprotectant in multiple sclerosis
  • Cytokine-directed therapies in MS
  • Dalfampridine in MS
  • Dimethyl fumarate and diroximel fumarate
  • DNA vaccine for MS
  • Erythropoietin as a neuroprotective in MS
  • Evobrutinib
  • Fingolimod
  • Fusokine composed of GM-CSF and IL-15 for immune suppression
  • Gene therapy for MS
  • Hookworm treatment for relapsing MS
  • Ibudilast for MS
  • Interferons
  • Iron chelators
  • IVIG for MS
  • Kinase inhibitors
  • Laquinimod
  • Melatonin for MS
  • Minocycline for MS
  • Monoclonal antibodies for MS
  • Natalizumab
  • Natural human antibodies for repair of myelin
  • Neurotrophic factors for multiple sclerosis
  • Nimodipine
  • Oral immunomodulatory agents for MS
  • Protein kinase Cβ as a therapeutic target for stabilizing BBB in MS
  • Recombinant T-cell ligands
  • Siponimod
  • Statins for MS
  • Teriflunomide
  • Tolerance-directed immunotherapy for MS
  • Ursolic acid
  • Concluding remarks and future prospects for neuroprotection in MS
  • Neuroprotection in anti-NMDA receptor encephalitis
  • Neuroprotection in transverse myelitis
  • Neuroprotection in decompression sickness
  • Neuroprotection in victims of drowning
  • Neuroprotection in CSF circulatory disorders
  • Neuroprotection in hydrocephalus
  • Neuroprotection in normal pressure hydrocephalus
  • Neuroprotection in cerebral edema
  • Pathomechanism and types of cerebral edema
  • Causes of cerebral edema
  • Principles of management of cerebral edema
  • Guidelines for management of acute cerebral edema
  • Neuroprotection in infections of the CNS
  • Neuroprotection in bacterial meningitis
  • Mechanism of neural injury in bacterial meningitis
  • Strategies for neuroprotection
  • Neuroprotection in progressive multifocal leukoencephalopathy
  • Neuroprotection in cryptococcal meningitis
  • Neuroprotective approach to rabies
  • Neuroprotection in cerebral malaria
  • Neuroprotection in neuroinflammation
  • Role of antiinflammatory drugs in the management of neuroinflammation
  • Nanoparticles for targeted delivery of antiinflammatory drugs
  • Personalized management of neuroinflammation
  • Neuroprotection in complications of systemic disorders
  • Neurological complications of cardiovascular disorders
  • Neuroprotection after myocardial infarction
  • Neuroprotection in hypertensive encephalopathy
  • Management of hypertension to prevent dementia
  • Neuroprotection in complications of diabetes
  • Neuroprotection in hypoglycemic coma
  • Neuroprotection in diabetic ketoacidosis
  • Neuroprotection in diabetic retinopathy
  • Neurological complications of liver disorders
  • Hepatic encephalopathy
  • Bilirubin encephalopathy
  • Neuroprotection in neurological complications of renal disease.
  • Neuroprotection in fever
  • Pharmacologic approaches for fever
  • Cooling the brain for neuroprotection
  • Neuroprotection in toxic encephalopathies
  • Encephalopathy due to organophosphorus poisoning
  • Sarin gas
  • Neuroprotection against chemotherapy-induced brain damage
  • Neuroprotection against alcohol
  • Alcoholic neurologic disorders
  • Fetal alcohol syndrome
  • Pathogenesis of alcohol-induced damage to the nervous system
  • Neuroprotection against neurotoxicity of alcohol
  • Neuroprotection against exposure to therapeutic radiation
  • Neuroprotection against radiation encephalopathy
  • Role of SOD in protection again radiation-induced hippocampal dysfunction
  • Catalase reduces mitochondrial ROS for neuroprotection from proton irradiation
  • Neuroprotection of the fetus and the neonate
  • Neuroprotection in preterm babies
  • Neuroprotection in neonatal hypoxic-ischemic brain injury
  • Pathomechanism of neonatal hypoxic-ischemic brain injury
  • Management of neonatal hypoxia-ischemia
  • Approaches to neuroprotection in neonatal hypoxia-ischemia
  • Hyperbaric oxygen for neonatal hypoxia-ischemia
  • Hypothermia for neonatal hypoxia-ischemia
  • Melatonin for neonatal hypoxia-ischemia
  • Minocycline for neonatal hypoxia-ischemia
  • Nicotinamide mononucleotide adenylyl transferase 1
  • Nitric oxide inhalation for neonatal hypoxia-ischemia
  • Plasminogen activator inhibitor-1 for neonatal hypoxia-ischemia
  • Recombinant erythropoietin for neonatal hypoxia-ischemia
  • Neuroprotection in carbon monoxide poisoning
  • Pathomechanism of CO poisoning as a basis for neuroprotection
  • Management of CO poisoning
  • Neuroprotection after cardiac arrest
  • Neuroprotection in delayed post-hypoxic leukoencephalopathy
  • Neuroprotection in sleep apnea
  • Neuroprotection in mitochondrial dysfunction
  • Mitochondrial permeability transition
  • Mitochondrial approaches for neuroprotection
  • Methylene blue
  • Mitochondrial encephalopathies
  • Neuroprotection in mitochondrial encephalopathies
  • Neuroprotection in psychiatric disorders
  • Electroconvulsive therapy and neuroprotection
  • Neuroprotection in schizophrenia
  • Cognitive impairment in schizophrenia
  • Neuroprotection in stress-induced neuropsychiatric disorders
  • Adenosine A2A receptor antagonists for neuroprotection in stress
  • Role of neurotrophic factors in stress-induced psychiatric disorders
  • Stress and dementia
  • Neuroprotection in hearing loss
  • Causes of hearing loss
  • Pathomechanism of hearing loss
  • Prevention and treatment of hearing loss
  • Hyperbaric oxygen for hearing loss
  • Stem cell therapy for sensory hearing loss
  • Gene therapy for sensorineural hearing loss
  • Pharmaceutical approaches to hearing loss
  • Prevention of drug-induced hearing loss
  • Neuroprotection of peripheral nerves
  • Neuroprotective agents for peripheral nerves
  • Acetyl-L-carnitine for peripheral nerve injuries
  • Atorvastatin for peripheral nerve injuries
  • Erythropoietin for neuroprotection in peripheral nerve injuries
  • Neuroprotection in peripheral nerve injuries
  • Role of hyperbaric oxygen in peripheral nerve injuries
  • Role of neurotrophic factors in peripheral nerve injuries
  • Pharmacological approaches to Schwann cells
  • Role of gene therapy in neuroprotection of injured peripheral nerves
  • Schwann cell transplantation for peripheral nerve injury
  • Targeting Wallerian degeneration slow protein for neuroprotection
  • Peripheral neuropathy
  • Neuroprotection in diabetic neuropathy
  • Cell therapy for neuroprotection in diabetic neuropathy
  • Gene therapy in diabetic neuropathy
  • Neuroprotection in chemotherapy-induced neuropathy
  • Neuroprotection in chronic inflammatory demyelinating polyradiculoneuropathy
  • Neuroprotection in Charcot-Marie-Tooth disease 1A

12. Neuroprotection of the Optic nerve and the Retina

  • Introduction
  • Optic neuropathy
  • Pathophysiology
  • Neuroprotection in optic neuritis
  • Azathioprine
  • Flupirtine
  • Eculizumab for neuromyelitis optica
  • Sodium channel blockers
  • Resveratrol
  • Satralizumab
  • Neuroprotection in optic nerve trauma
  • Potential regeneration of the optic nerve
  • Neuroprotection of optic nerve in glaucoma
  • Aminoguanidine as a neuroprotective in glaucoma
  • Antiglutamate agents for neuroprotection of optic nerve
  • Betaxolol
  • NGF eye drops
  • Targeting Aβ in glaucoma treatment
  • TNF-α blockers for neuroprotection in glaucoma
  • Concluding remarks about neuroprotection in glaucoma
  • Neuroprotection in retinal ischemia
  • β-adrenoceptor antagonists
  • Brimonidine as a neuroprotective is ischemic retinopathy
  • Endogenous neuroprotection in the retina
  • Erythropoietin for neuroprotection of retinal ischemia
  • Gene therapy for retinal neuroprotection
  • Hyperbaric oxygen for central retinal artery occlusion
  • Levodopa for treating non-arteritic anterior ischemic optic neuropathy
  • Thioredoxin as a neuroprotective agent in retinal ischemia
  • Protection against oxygen-induced retinopathy
  • Neuroprotection in macular degeneration
  • Epidemiology
  • Pathomechanism of AMD
  • Current treatment of AMD
  • Novel neuroprotective strategies against retinal degeneration
  • Antiangiogenic agents
  • Humanized MAb against Aβ
  • LXR agonists
  • Neurotrophic factors for neuroprotection in AMD
  • CNTF for neuroprotection in AMD
  • N-acetylserotonin derivatives
  • Nutritional protection against AMD
  • Progestogenic hormones
  • Protection of retinal cells from oxidative-stress-induced apoptosis
  • Sulindac
  • Tandospirone
  • Cell therapy for macular degeneration
  • Retinal pigment epithelial cells
  • Stem cell transplantation in the retina
  • Neural progenitor cells
  • hESC-derived RPE cells for AMD
  • Gene therapy for retinal degeneration
  • Combining stem cell and gene therapies for retinal disorders
  • RNAi-based treatments for AMD
  • Neuroprotection in proliferative diabetic retinopathy
  • RNAi-based approaches to diabetic retinopathy
  • Clinical trials for optic nerve and retinal neuroprotection

13. Neuroprotection during Anesthesia and Surgery

  • Introduction
  • Anesthetic agents as neuroprotectives
  • Barbiturates
  • Thiopental
  • Etomidate
  • Propofol
  • Ketamine
  • Gaseous anesthetics
  • Isoflurane
  • Xenon
  • Local anesthetics
  • Monitoring of CNS function during anesthesia and surgery
  • Monitoring of cerebral function
  • Monitoring of spinal cord function during spinal surgery
  • Perioperative neuroprotection
  • Neuroprotection during cardiovascular procedures
  • CNS complications of cardiac surgery
  • Neuroprotective strategies during cardiac surgery
  • Neuroprotection before anticipated or induced cardiac arrest
  • Neuroprotection during coronary artery bypass grafting
  • Preconditioing with hyperbaric oxygen
  • Neuroprotection in aortic surgery
  • Pharmacologic strategies for neuroprotection in aortic surgery
  • Cerebral protection during organ transplantation surgery
  • Cerebral protection in neurosurgery
  • Cerebral angiography and endovascular surgery
  • Cerebral protection during surgery for arteriovenous malformations
  • Cerebral protection during surgery of intracranial aneurysms
  • Management of subarachnoid hemorrhage
  • Vasospasm associated with subarachnoid hemorrhage
  • Cerebral protection during carotid endarterectomy
  • Cerebral protection during surgery of brain tumors
  • Neuroprotective measures prior to surgery
  • HBO preconditioning for neuroprotection during surgery
  • Neuroprotection following surgery
  • Neuroprotection by cranioplasty after decompressive craniectomy

List of Tables
Table 1-1: Historical landmarks in the development of neuroprotection
Table 1-2: Intrinsic neuroprotective factors
Table 1-3: Common features of pathophysiology of brain damage in diseases
Table 1-4: Place of neuroprotection in management of CNS disorders
Table 1-5: Indications for the use of neuroprotection
Table 1-6: Neuroprotective nanoparticles
Table 2-1: A classification of neuroprotective agents
Table 2-2: The neuroprotective effect of antiepileptic drugs
Table 2-3: Neuroprotective affect of minocycline in animal models
Table 2-4: Classification of antioxidants or free radical scavengers with neuroprotective potential
Table 2-5: Role of erythropoietin in the nervous system
Table 2-6: Ionotropic glutamate receptors
Table 2-7: Classification of metabotropic glutamate receptors (mGluRs)
Table 2-8: Methods for neuroprotection based on nonpharmacological preconditioning
Table 3-1: Cerebrovascular diseases that are relevant to neuroprotection
Table 3-2: Neuroprotective strategies for stroke
Table 3-3: Selected effective combinations of hypothermia with other neuroprotective strategies
for the treatment of ischemic stroke in experimental models
Table 3-4: Neuroprotective gene transfer in models of cerebral ischemia
Table 3-5: Neuroprotective gene therapy in animal stroke models
Table 3-6: Neuroprotective agents in clinical development for acute cerebrovascular disease
Table 3-7: Some failed trials for neuroprotective therapy for stroke
Table 3-8: Preclinical assessment of neuroprotective agents in acute stroke models
Table 3-9: Stroke prevention based on control of risk factors
Table 4-1: Classification of closed TBI
Table 4-2: Pathophysiologic responses to TBI and for neuroprotective strategies
Table 4-3: Current conventional management of traumatic brain injury
Table 4-4: Neuroprotective strategies for traumatic brain injury
Table 4-5: Intrinsic factors that influence regeneration in the central nervous system
Table 4-6: A classification of approaches to regeneration of the brain following injury
Table 4-7: Ongoing or completed clinical trials for neuroprotection in TBI
Table 4-8: Discontinued or failed clinical trials for neuroprotection in TBI
Table 5-1: Secondary mechanisms in spinal cord injury
Table 5-2: Neuroprotective and regenerative approaches for SCI
Table 5-3: Clinical trials for neuroprotection in SCI
Table 6-1: Neurodegenerative disorders with dementia
Table 6-2: Drugs in clinical trials for spinal muscular atrophy
Table 6-3: Pharmacological approaches to neuroprotection in CJD
Table 6-4: Glutamate-based therapies in clinical development for neurodegenerative disorders
Table 7-1: Prevalence of Parkinson's disease in major markets 2019-2029
Table 7-2: Factors in the etiology of Parkinson's disease
Table 7-3: Strategies for the treatment of Parkinson's disease
Table 7-4: Gene therapy techniques applicable to Parkinson disease
Table 7-5: Current clinical trials of neuroprotective therapies for Parkinson disease
Table 7-6: Failed clinical trials of neuroprotective therapies for Parkinson disease
Table 7-7: Evaluation of neuroprotective agents for PD
Table 8-1: Relation of mutations in amyloid precursor protein to CNS disorders
Table 8-2: Risk factors for Alzheimer's disease
Table 8-3: Cholinergic approaches to the treatment of Alzheimer's disease
Table 8-4: Neuroprotective approaches to Alzheimer's disease
Table 8-5: Clinical trials in Alzheimer disease
Table 8-6: Discontinued, failed or inconclusive clinical trials of Alzheimer disease
Table 8-7: Strategies for discovery of neuroprotective therapies for AD
Table 9-1: Neuroprotective approaches in HD
Table 10-1: Hypotheses for the pathogenesis of amyotrophic lateral sclerosis
Table 10-2: Genetic diagnostic biomarkers of ALS
Table 10-3: Classification of neuroprotective agents for amyotrophic lateral sclerosis
Table 11-1: Therapeutic approaches to subcortical vascular dementia
Table 11-2: Measures for neuroprotection against the sequelae of seizures
Table 11-3: Neuroprotective effect of AEDs in animal models of status epilepticus (SE)
Table 11-4: Specific therapies for MS based on postulated pathomechanisms
Table 11-5: Approved neuroprotective/neuromodulating therapies for multiple sclerosis
Table 11-6: Neuroprotective therapies for multiple sclerosis in clinical trials
Table 11-7: Causes of cerebral edema
Table 11-8: Principles of management of cerebral edema
Table 11-9: Methods for management of neuroinflammation
Table 11-10: Measures to prevent acute bilirubin encephalopathy
Table 11-11: Fever associated with neurologic disorders
Table 11-12: Approaches to neuroprotection in neonatal hypoxia-ischemia
Table 11-13: Drugs with neuroprotective effect at mitochondrial level
Table 11-14: Causes of sensorineural hearing impairment
Table 11-15: Strategies for prevention and treatment of sensorineural hearing loss
Table 11-16: Agents for neuroprotection of the peripheral nervous system
Table 11-17: Neuroprotective agents for chemotherapy-induced peripheral neuropathy
Table 12-1: Causes of optic neuropathy
Table 12-2: Clinical trials of neuroprotective therapies in optic neuritis
Table 12-3: Neuroprotection of the optic nerve in glaucoma
Table 12-4: Strategies for neuroprotection in retinal ischemia
Table 12-5: Novel neuroprotective strategies against retinal degeneration
Table 12-6: Clinical trials for retinal neuroprotection
Table 13-1: CNS complications associated with cardiac procedures
Table 13-2: Strategies for protection of the brain during cardiac surgery
Table 13-3: Medical and surgical methods of cerebral vasospasm management
Table 13-4: Neuroprotection by prevention of vasospasm

List of Figures
Figure 1-1: A three-stage model of ischemic hypoxic disturbances of the brain
Figure 2-1: Mechanism of neuroprotective effect of sigma-1 receptor agonists
Figure 2-2: NMDA receptor ion channel complex
Figure 2-3: Neuroprotective effect of galantamine
Figure 3-1: Some steps in the ischemic cascade and site of action of neuroprotectives
Figure 3-2: Relationship between dementia and acute ischemic stroke
Figure 3-3: Pathomechanism of ischemic stroke and neuroprotective strategies
Figure 3-4: Molecules involved in preconditioning for neuroprotection in ischemia
Figure 3-5: A roadmap for neuroprotection
Figure 4-1: Cascade of events following traumatic brain injury
Figure 4-2: Neurometabolic cascade of mild TBI
Figure 4-3: Secondary injury mechanisms after TBI
Figure 4-4: Management of raised ICP after TBI
Figure 5-1: Pathomechanism of acute spinal cord injury
Figure 6-1: Identification of protein targets in neurodegenerative disorders
Figure 7-1: Neuroprotective strategies against death of damine-containing neurons in PD
Figure 8-1: Mechanisms of Aβ clearance
Figure 8-2: Nitric oxide neurotoxicity and neuroprotection in relation to Alzheimer disease
Figure 8-3: Oxidative stress and Alzheimer disease
Figure 8-4: Pathomechanism of AD
Figure 9-1: Role of HTT protein in pathogenesis of HD and points of intervention
Figure 11-1: A schematic overview of synaptopathies
Figure 11-2: Common mechanisms of neural damage in cerebral ischemia and seizures
Figure 11-3: Role of neuroprotection in epilepsy and its treatment
Figure 11-4: Mechanisms of neonatal hypoxia-ischemia and targets for neuroprotection

Part II: Markets and Companies

14. Markets for Neuroprotective Therapies

  • Introduction
  • The financial burden of CNS damage
  • Markets for neuroprotective therapies
  • Markets according to therapeutic areas
  • Stroke
  • CNS injury
  • Alzheimer disease
  • Parkinson disease
  • Multiple sclerosis
  • Epilepsy
  • Values of neuroprotective therapies in major world markets
  • Unmet needs in neuroprotectives
  • Future of neuroprotective therapies
  • Challenges in neuroprotective drug development
  • Promising areas of research in neuroprotection
  • Autoreactive antibodies
  • Biological therapies for neuroprotection
  • Multidisciplinary approaches to neuroprotection

15. Companies Developing Neuroprotective Therapies

  • Introduction
  • Profiles of companies
  • Collaborations

16. References

List of Tables
Table 14-1: Neuroprotective market values 2020-2030
Table 14-2: Values of neuroprotective therapies in major world markets from 2020-30
Table 15-1:Pipeline of Alkahest
Table 15-2: Collaborations of companies in the area of neuroprotection

List of Figures
Figure 14-1: Unmet therapeutic needs in neuroprotective therapies
Figure 15-1: Neurovive’s pipeline

Note: Product cover images may vary from those shown
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