Neuroprotection - Methods, Drugs, Markets and Companies

Table of Contents

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

Samples