Abstract
Summary
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 136 companies that have a neuroprotective
product or products along with 120 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 850 references are included, a considerable amount of information
has not been published anywhere else. 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 67 tables and 13 figures.
Market analysis of currently used products that have a neuroprotective effect
are analyzed for the year 2012. Some of these products are approved for other
indications but are known to have a neuroprotective effect. With the approval
of new products and takeover of markets for obsolete symptomatic therapies,
the neuroprotection market value will rise by the year 2017 when it will
constitute a major and important component of the CNS market. Forecasts are
made until 2022. By that time neuroprotection will be an established part of
the neurological practice and measures will be available to achieve this
effectively.
Table of Contents
PartI
0. Executive Summary 25
1. Introduction 29
- Definitions 29
- Historical development of neuroprotection 29
- Intrinsic neuroprotective factors 30
- Neuroprotective gene expression 31
- Upregulation of GADD34 31
- Induction of NR4A proteins by CREB in neurons 32
- Neurotrophic factors 32
- Intrinsic nonenzymatic antioxidants 32
- Activation of transcription factor Nrf2 33
- Intrinsic neuroprotective proteins 33
- αB-crystallin 33
- Excitatory amino acid transporters 33
- Extracellular serine protease thrombin 33
- Galanin 34
- Neuroglobin 34
- Nuclear factor I-A 34
- Prion protein 35
- Rai adaptor protein 35
- Stem cell factor 35
- Role of the immune system in neuroprotection 36
- Induction of DNA repair enzymes for neuroprotection 36
- Microtubule-based neuroprotective response to axonal injury 37
- Pathomechanisms of CNS injury as basis for neuroprotection 37
- Biomarkers of neurological disorders and neuroprotection 38
- CNS biomarker identification using proteomics 38
- Brain imaging for detection of biomarkers 38
- Role of neuroprotection in various neurological disorders 38
- Neuroprotection and neuroregeneration 40
- Acute versus chronic neuroprotection 40
- Discovery and evaluation of neuroprotective agents 40
- Neuroprotective drug discovery 40
- Discovery of CNS drugs that penetrate the blood-brain barrier 41
- In vitro assays for the evaluation of neuroprotective agents 41
- Oxidative injury model to test neuroprotective drugs 42
- Apoptosis model for designing neuroprotective drugs 42
- Transgenic mouse models of neurological disorders 42
- Evaluating effects of neuroprotective drugs on living brain slices
43
- Role of brain imaging in neuroprotective drug discovery and development
43
- Positron emission tomography 44
- Role of single photon emission computed tomography 44
- Functional CT scanning to evaluate cerebrovascular protection 44
- Magnetic resonance imaging for the evaluation of neuroprotectives
45
- Application of nanotechnology to neuroprotection 45
- Evaluation criteria for potential neuroprotective agents 45
2. Neuroprotective Agents 47
- Classification of neuroprotective agents 47
- α2 adrenoreceptor agonists 51
- Dexmedetomidine 51
- Activated protein C 52
- Activity-dependent neuroprotective protein 52
- Davunetide 52
- Adenosine analogs 52
- Propentofylline 53
- Antidepressants 53
- Antidepressant-induced neurogenesis 53
- Neurogenesis induced by electroconvulsive therapy 54
- Neuroprotective effect of selective serotonin reuptake inhibitors
54
- Antiepileptic drugs as neuroprotectives 56
- Phenytoin 57
- Valproic acid 57
- Levetiracetam 57
- Antiinflammatory agents 58
- Aspirin 58
- Interleukin-1 antagonists 58
- COX-2 inhibitors 59
- Nimesulide 59
- Gold microparticles as anti-neuroinflammatory agents 59
- Minocycline 59
- Prostaglandin receptor antagonists 60
- Anti-apoptosis agents 61
- Activated protein C 62
- Calpain inhibitors 62
- Caspase inhibitors 62
- DNA binding drugs 62
- Lithium 63
- Olesoxime 63
- Omega-3 fatty acids 63
- Docosahexaenoic acid 64
- Poly(ADP-ribose) polymerase inhibitors 64
- Prevention of apoptosis by binding of proNGF to sortilin 65
- Antioxidants/free radical scavengers 65
- Free radical generation 65
- Natural defenses against oxidative stress 66
- Effects of oxidative damage 66
- Oxidative damage and aging 66
- Neuronal damage by free radicals 67
- Oxidative damage and neurodegenerative disorders 67
- Measures to control oxidative stress 67
- Categories of therapeutic antioxidants 67
- Alpha-phenyl-tert-butylnitrone 68
- Coenzyme Q10 68
- Dihydroergocryptine 69
- Flavonoids 69
- Mitochondria-targeted antioxidants 70
- Nanoparticles as neuroprotective antioxidants 70
- Neuroleptics as antioxidants 71
- Nitrones 71
- Translation of antioxidant neuroprotection from preclinical to clinical
71
- Carbon monoxide and heme oxygenase 72
- Cell transplants 72
- Cells secreting neuroprotective substances 72
- Stem cells 73
- Stem cell activation for neuroprotection/regeneration by glucocorticoids
73
- Cytokines 73
- Erythropoietin 73
- Non-erythropoietic EPO variants and mimics 75
- Granulocyte colony-stimulating factor 75
- Delta-opioid receptor agonists 76
- FK960 76
- Gene therapy 76
- Glucagon-like peptide 77
- Glatiramer acetate 78
- Glutamate antagonists 78
- Neuroprotection by scavenging blood glutamate 79
- N-acylethanolamines for protection against glutamatergic excitotoxicity
79
- Glutamate transporters 80
- Glutamate transporter-mediated neuroprotective effect of drugs 80
- Neuroprotection by targeting KAI subunit of kainate receptor 80
- Glycine-proline-glutamate analogs 81
- Herbal preparations 81
- Flavonoid wogonin 81
- Ginseng 82
- Hydrogen sulfide 82
- NMDA receptor ion channel complex 82
- NMDA receptor antagonists 84
- NMDA NR2B subunit receptor antagonists 84
- Ifenprodil 84
- Memantine as a neuroprotective agent 84
- Magnesium 84
- NAALADase inhibitors 85
- Gacyclidine 85
- N-alkylglycines 85
- AMPA receptor modulators 86
- Metabotropic glutamate receptor modulators 86
- Cannabinoids 87
- Dexanabinol 87
- Glutathione 88
- Heat shock proteins 88
- Hormones 88
- Estrogen and neuroprotection 88
- Neuroprotective effect of estrogen receptor ligands 89
- Selective estrogen receptor modulators 89
- Mitochondrial mechanisms of estrogen neuroprotection 90
- Insulin 90
- Ion Channel modulators 91
- Calcium channel blockers 91
- Ziconotide 91
- Na+ channel blockers 92
- Neuroprotective potassium channel inhibitors 92
- Kynurenine inhibitors 93
- Leukocyte adhesion inhibitors 93
- Modafinil 94
- Neural regeneration protein 94
- Neurite outgrowth-promoting prostaglandin compounds 94
- Neuroimmunophilins 95
- Cyclosporin-A 95
- FK506 96
- Rapamycin 96
- Neurotrophic factors 96
- Activity-dependent neurotrophic factor 97
- Bone morphogenetic proteins 97
- Brain-derived neurotrophic factor 97
- Ciliary neurotrophic factor 98
- Fibroblast growth factors 98
- Glial cell line-derived neurotrophic factor 99
- Insulin-like growth factor 99
- Nerve growth factor 100
- Neurotrophins 100
- Osteogenic protein-1 101
- Pigment epithelium-derived factor 101
- Transforming growth factor-β1 101
- Vascular endothelial growth factor 101
- Neurotrophic factor-related neuroprotective agents 102
- Amitriptyline as a TrkA and TrkB receptor agonist 102
- Colivelin 102
- Gambogic amide 102
- Inosine 103
- Meteorin 103
- Oxygen-regulated protein 150 kD 103
- Prosaptide 103
- Siagoside 104
- Small molecule activators of the Trk receptors 104
- Nicotine and nicotinic receptor agonists 105
- Neuroprotective effect of galantamine mediated via α7nAChRs
105
- Galantamine-induced Aβ clearance via α7nAChRs 105
- Nitric oxide-based neuroprotection 106
- Nitric oxide synthase inhibitors 106
- Nitric oxide mimetics 107
- Nitric oxide donating derivatives 107
- Nootropics 107
- Piracetam 108
- Nutraceuticals and food constituents 108
- Coffee 108
- Creatine 109
- Curcumin/curry 109
- Mechanism of neuroprotective effect of curcumin 109
- Flavonoids 110
- Glyceryltriacetate 110
- Green tea 110
- Nicotinamide 110
- Resvatrol 111
- Osmotic diuretics 111
- Mannitol 111
- Osteopontin 112
- Oxygen therapeutics 112
- Oxygen carriers 113
- Hemoglobin-based oxygen carriers 113
- Perfluorocarbons as oxygen carriers 113
- Hyperbaric oxygen therapy 114
- Peptides 114
- C3-derived peptide for neuroprotection and neuroregeneration 115
- Corticotropin-releasing hormone 115
- Thyrotropin-releasing hormone 115
- Vasoactive intestinal peptide 116
- Pharmacological preconditioning 116
- PPARs as drug targets for neuroprotection 116
- Riluzole 117
- Role of RNA interference in neuroprotection 117
- Sigma receptor agonists as neuroprotective agents 118
- SIRT group of proteins 118
- Statins 119
- Steroids 120
- Dehydroepiandrosterone 120
- HF0220 120
- Sulforaphane 121
- Tauroursodeoxycholic acid 121
- Tetanus toxin as a neuroprotective agent 121
- Thrombolytic agents as neuroprotective agents 121
- Uncoupling protein 2 122
- Vaccines as neuroprotectives 122
- Vitamins as neuroprotective agents 122
- Vitamin B12 123
- Vitamin D 123
- Non-pharmacological approaches to neuroprotection 123
- Environmental enrichment 124
- Mental training 124
- Physical exercise 124
- Hypothermia 124
- Limitations of hypothermia 125
- Hypothermic neuroprotection in hypoxia-ischemia 125
- Hibernation induced by hydrogen sulfide 126
- Ketogenic diet 126
- Nonpharmacological preconditioning for neuroprotection 127
- Transcranial magnetic stimulation 127
- Electrical fields for improvement of cerebral function in
neurodegeneration 128
- Neuroprotective effect of exercise 129
- Hibernation and neuroprotection 129
- Suspended animation and neuroprotection 129
3. Neuroprotection in Cerebrovascular Disease 131
- Introduction 131
- Pathophysiology of cerebral ischemia 131
- Calcium overload 132
- Ion channel dysfunction in stroke 132
- Role of oxygen free radicals in cerebral ischemia 133
- Role of nitric oxide in cerebral ischemia 133
- Glutamate as a biomarker of stroke 133
- Cerebral edema in stroke 133
- Gene expression in response to cerebral ischemia 134
- Induction of heat shock proteins in stroke 134
- Role of cytokines and adhesion molecules in stroke 134
- Tumor necrosis factor-α 135
- Interleukin-1 and IL-6 135
- Adhesion molecules 135
- DNA damage and repair in cerebral ischemia 135
- Role of neurotrophic factors in stroke 136
- Problems requiring investigation of the role of NTFs in stroke 136
- Role of Poly(ADP-ribose) polymerase (PARP) gene 136
- Role of protease-activated receptor 1 137
- Reperfusion injury after cerebral ischemia 137
- Neuroprotection according to zones in cerebral infarction 137
- Zone of ischemic infarction 137
- Penumbra 138
- Current management of stroke 138
- Neuroprotection in stenosis of intracranial arteries 139
- Neuroprotection in transient ischemic attacks 139
- Secondary prevention of stroke 139
- Neuroprotective therapies for stroke 140
- αB-crystallin as a neuroprotectant in stroke 141
- Acid-sensing ion channel blockers 141
- AMPA receptor antagonists as neuroprotectives for stroke 141
- Zonampanel 141
- Antiapoptotic neuroprotectives 141
- NIM811 142
- Creatine as neuroprotective in stroke 142
- Lithium as a neuroprotective in stroke 142
- TUDCA as a neuroprotective in stroke 142
- Antiepileptic drugs as neuroprotectives in stroke 143
- Tiagabine 143
- Topiramate 143
- Zonisamide 143
- Anti-HMGB1 monoclonal antibody 144
- Antioxidant approaches 144
- Carnosine as a neuroprotective in stroke 144
- Dehydroascorbic acid 145
- Tocotrienols 145
- Uric acid 146
- Antiglutamate compounds 146
- MRZ 2/576 146
- L-Phenylalanine 146
- Arimoclomol for stroke 147
- Cardiac glycosides as neuroprotectives in stroke 147
- Clenbuterol 147
- Coagulation inhibitors as neuroprotectives 147
- Heparin and enoxaparin 148
- Warfarin vs dabigatran 148
- Apixaban 148
- Cox-2 inhibitors for ischemic stroke 148
- Curcumin as a neuroprotectant in stroke 149
- Docosahexaenoic acid for ischemic stroke 149
- Ephrin-A5 blockers 149
- Estrogen for stroke 150
- Extendin-4 151
- Flavones for neuroprotection in stroke 151
- Granulocyte-macrophage colony-stimulating factor for cerebral ischemia
152
- Hamartin induction by cerebral ischemia as a basis for neuroprotection
152
- Modulation of histamine H2-receptors 152
- Inosine for stroke 153
- Insulin-like growth factor-I 153
- Intravenous immunoglobulin as neuroprotective in stroke 153
- Ischemic preconditioning for neuroprotection in stroke 153
- Ketone bodies for neuroprotection in stroke 154
- Mineralocorticoid receptor blockade for neuroprotection 154
- miR-223 and neuroprotection in stroke 155
- Multifunctional neuroprotective agents 155
- NA-1 as neuroprotective against ischemic stroke 155
- Nasal delivery of neuroprotective agents in stroke 155
- Neuroserpin as a neuroprotective in stroke 156
- N-2-mercaptopropionyl glycine 156
- NeuroAid 156
- Neurotrophic factors as neuroprotectives for stroke 157
- AX200 157
- Brain-derived neurotrophic factor 157
- Fibroblast growth factor 158
- Glial cell line-derived neurotrophic factor 158
- Insulin-like growth factor-1 158
- Neuregulin-1 158
- NO-based strategies for neuroprotection in cerebral ischemia 159
- Pannexin channel blockers for neuroprotection in stroke 159
- Perlecan domain V 160
- Peroxisome proliferator-activated receptor-γ agonists
160
- PGE2 EP2 receptor activation 160
- Pioglitazone for reduction of stroke risk in diabetes 160
- Progesterone 160
- Propofol as neuroprotective in stroke 161
- Proteoglycan-degrading enzymes 161
- Proteosome inhibitors 161
- Statins for prevention and neuroprotection in stroke 162
- Sildenafil 162
- Src receptor blockade 163
- Stroke vaccine 163
- SUN N4057 163
- Thrombosis inhibitors 164
- Aspirin 164
- Clopidogrel 164
- Dipyridamole 164
- Vitamin E for neuroprotection in stroke 164
- Neuroprotection in reperfusion injury 165
- Prevention of hemorrhage following ischemic stroke 166
- Non-pharmacological neuroprotective therapies for stroke 166
- Preconditioning for neuroprotection against cerebral ischemia 166
- Hypothermia for neuroprotection in acute stroke 166
- Hyperbaric oxygen therapy for neuroprotection in acute stroke 167
- Infrared laser therapy for ischemic stroke 168
- Neurostimulation of sphenopalatine ganglion 168
- Neurosurgical procedures for neuroprotection in stroke 169
- Neurorehabilitation in relation to neuroprotection in stroke 170
- Cell therapy for stroke 170
- Stem cell transplant for stroke 170
- Immortalized cell grafts for stroke 171
- Stimulation of instrinsic stem cells for repair of brain in stroke
171
- Neuroprotective vaccines for stroke 171
- Gene therapy for neuroprotection in cerebrovascular disease 172
- Regulation of microRNAs for neuroprotection in cerebral ischemia
174
- RNAi-based therapy for neuroprotection in stroke 174
- Neuroprotective therapies for cerebral ischemia: clinical trials
174
- Albumin 175
- Free radical scavengers 175
- DP-b99 177
- Mildronate 177
- Minocycline for neuroprotection in stroke 177
- Perindopril 178
- Failed clinical trials of neuroprotection in stroke 178
- Ancrod 180
- Aptiganel 180
- Cerovive 180
- Citicoline 181
- Desmoteplase 182
- Erythropoietin as a neuroprotective in stroke 183
- SPD 502 183
- Tirilazad mesylate 183
- Selfotel 184
- Lubeluzole 184
- Nalmefene 184
- Gavestinel 184
- Nimodipine 185
- Sipatrigine 185
- Causes of failure of stroke trials 185
- Measures for prevention of failures in stroke trials 187
- Design of acute stroke trial to facilitate drug approval 188
- The ideal neuroprotective agent for stroke 189
- Future prospects for neuroprotection in stroke 189
4. Neuroprotection in Traumatic Brain Injury 191
- Introduction 191
- Cerebral hypoxia/ischemia as a complication of trauma 191
- Epidemiology of TBI 191
- TBI in the military 192
- Pathophysiology of TBI 192
- Immediate damage following TBI 193
- Cerebral edema following TBI 193
- Delayed damage following TBI 193
- Mechanism of axonal damage after TBI 193
- Role of neuroinflammation in TBI 193
- Molecular events following TBI 194
- BBB damage after TBI 194
- Chronic traumatic encephalopathy 194
- Neurocognitive sequelae of TBI 195
- Changes in neurotrophic factors following TBI 196
- Changes in neurotransmitters following TBI 196
- Proteomics of TBI 196
- Genetic influences on outcome following TBI 197
- Management of TBI 197
- Control of intracranial pressure and cerebral edema 198
- Corticosteroids 198
- Neuroprotection in TBI 199
- Amantadine 200
- Antiepileptic drugs for prevention of seizures and neuroprotection
200
- Antioxidants 200
- Barbiturates 201
- β- and γ-secretase inhibitors 201
- Beta blockers 201
- Bradykinin B2 antagonists 202
- Cell cycle inhibitors for TBI 202
- COX-2 inhibitors for neuroprotection in TBI 202
- Cyclosporin for neuroprotection in TBI 203
- Dexanabinol for TBI 203
- Erythropoietin for neuroprotection in TBI 203
- Gold implants for neuroprotection in focal TBI 203
- KN 38-7271 204
- Levosimendan 204
- Magnesium sulfate 204
- Minocycline for TBI 204
- Nutritional approaches to neuroprotection in TBI 205
- Branched chain amino acids to ameliorate cognitive impairment in TBI
205
- Creatine for neuroprotection in TBI 205
- Nicotinamide for neuroprotection in TBI 206
- Omega 3 fatty acids as neuroprotectives in TBI 206
- Neurotrophic factors for TBI 207
- Neurosteroids as neuroprotective agents for TBI 207
- NMDA receptor antagonists 208
- NP-1 209
- Nogo-A inhibitor 209
- Oxygen carriers for TBI 209
- Polyethylene glycol for neuroprotection in TBI 210
- Propofol for neuroprotection in TBI 210
- Rapamycin as neuroprotective in TBI 210
- Simvastatin as neuroprotective in TBI 211
- Thyrotropin-releasing hormone analogs 211
- Traxoprodil 211
- Biological approaches to neuroprotection in TBI 212
- Antisense approaches to TBI 212
- Cell therapy for TBI 212
- Gene therapy for TBI 212
- Vaccines for TBI 213
- Non-pharmaceutical approaches to neuroprotection in TBI 213
- Hyperbaric oxygen therapy for TBI 213
- Hypothermia 213
- Reduction of microglial migration after TBI 213
- Deep brain stimulation for TBI 214
- Prophylactic neuroprotection against TBI 214
- Role of helmets in protection against TBI 214
- Role of physical exercise in protection against TBI 215
- Clinical trials of neuroprotective agents in TBI 215
- Ongoing clinical trials in TBI 215
- Failed clinical trials in TBI 216
- Differences between clinical trials and studies in animal models of TBI
217
- Subgroup analysis 217
- Improving the clinical trial design 218
- Clinical trials combining multiple treatment strategies 218
- Shortening the trial time 218
- Conclusions and future prospects of neuroprotection in TBI 218
5. Neuroprotection in Spinal Cord Injury 221
- Introduction 221
- Pathophysiology of SCI 221
- Secondary mechanisms of SCI 222
- Neurotrophic factor changes in SCI 223
- Management of SCI 224
- Pharmacological neuroprotective agents for SCI 225
- 4-aminopyridine 225
- Antibodies as neurite growth inhibitors in SCI 225
- Bacterial enzyme chondroitinase ABC 225
- Docosahexaenoic acid as neuroprotective in SCI 226
- Erythropoietin as a neuroprotective in SCI 226
- Free radical scavengers for neuroprotection in SCI 226
- Gacyclidine 227
- GYKI 52466 227
- Immunosuppressants as neuroprotectants in SCI 227
- Interleukin-10 for neuroprotection in SCI 227
- Matrix metalloproteinase inhibitors for SCI 228
- Methylprednisolone 228
- Minocycline as neuroprotective in SCI 228
- Neurotrophic factors for neuroprotection after SCI 229
- Promotion of regeneration of neurons in SCI 230
- Rho pathway and Rho antagonists in SCI 230
- Selenium as a neuroprotective for SCI 230
- Sialidase for enhancing recovery after SCI 231
- Targeting the inflammatory response for neuroprotection in SCI
231
- Uric acid as neuroprotective in SCI 231
- Non-pharmacological approaches to SCI 231
- Hyperbaric oxygen therapy 231
- Hypothermia for SCI 232
- Cell therapy for SCI 232
- Autoimmune T cells against CNS myelin-associated peptide 232
- Fetal neural grafts for SCI 232
- Olfactory-ensheathing cells for SCI 232
- Oligodendrocyte precursor cells for treatment of SCI 233
- Schwann cell transplants for SCI 233
- Transplantation of glial cells for SCI 233
- Stem cells for SCI 234
- Bone marrow stem cells for SCI 234
- Embryonic stem cells for SCI 234
- Transplantation of induced pluripotent stem cells in SCI 235
- Transplantation of MSCs for SCI 235
- Transplantation of NSCs for SCI 235
- Transdifferentiation of stem cells into cholinergic neurons for SCI
236
- Gene therapy for SCI 236
- Combined approaches to spinal cord injury 237
- Discovery of new targets for neuroprotective therapies in SCI 238
- Clinical trials in SCI 238
6. Neuroprotection in Neurodegenerative Disorders 241
- Introduction 241
- Pathomechanism of neurodegeneration 241
- Dual role of γ-synuclein in neuroprotection and neurodegeneration
241
- Lack of neurotrophic factors 242
- Neuroinflammation in neurodegenerative disorders 242
- Neurodegeneration associated with protein misfolding 242
- Modulation of neurodegeneration by molecular chaperones 242
- Intrabodies targeting protein misfolding in neurodegeneration 243
- Targeting proteins aggregation to prevent amyloid formation 243
- Tau and neurodegeneration 243
- Role of apoptosis in neurodegenerative disorders 244
- Role of glia in neurodegeneration 244
- Role of metals in neurodegeneration 244
- Spread of neurodegeneration 245
- TDP-43 proteinopathy and neurodegenerative diseases 245
- Viral infections and neurodegeneration 245
- AIDS and the nervous system 245
- Avian influenza as cause of neurodegeneration 247
- Neurodegenerative disorders with dementia 247
- Dementia with Lewy bodies 248
- Pick disease 248
- Progressive supranuclear palsy 249
- Genetic disorders with neurodegeneration 249
- Batten disease 249
- Friedrich ataxia 250
- Pathomechanism of FA 250
- Neuroprotection in FA 250
- Niemann-Pick type C disease 251
- Creutzfeldt-Jakob disease 251
- Potential neuroprotectants for CJD 251
- Approaches to neuroprotection in neurodegenerative disorders 252
- Glutamate-based therapies for neurodegenerative disorders 253
- Iron chelation for neuroprotection 253
- Mitochondria permeability transition pore complex and neuroprotection
253
7. Neuroprotection in Parkinson Disease 255
- Introduction 255
- Epidemiology of Parkinson's disease 255
- Pathophysiology of Parkinson's disease 255
- Oxidative stress 256
- Excitotoxicity 257
- Asynchronous neuronal activity 257
- Apoptosis 257
- Role of neurotrophic factors 257
- Role of misfolding proteins 257
- Genetic factors in PD 258
- Alteration of dopamine homeostasis 259
- Neuroprotective strategies for PD based on pathomechanism 260
- RNAi screening to identify neuroprotective genes in a PD model
261
- A genetic animal model of PD for testing neuroprotective strategies
262
- Management of Parkinson's disease 262
- Limitation of conventionally administered dopamine therapy 263
- Treatment of dementia associated with PD 264
- Neuroprotective therapy in PD 264
- Neuroprotective effect of currently used drugs for PD 265
- Pramipexole 265
- Rasagiline mesylate 266
- Ropinirole 266
- Selegiline 267
- Non-pharmacological strategies for neuroprotection in PD 267
- Effect of exercise and environmental enrichment on PD 267
- Low-calorie diet in PD 268
- Development of neuroprotective therapies for PD 268
- 2B3-201 for targeted delivery of methylprednisolone 268
- 9-methyl-β-carboline 268
- Adenosine AA2 receptor antagonists 269
- Antiapoptotic strategies for PD 269
- Augmenting CNS glucocerebrosidase activity 270
- Calcium channel blockers for PD 270
- Cell therapies for PD 270
- Stem cells for PD 270
- Activation of endogenous stem cells and neural precursors 271
- Cogane 272
- Creatine and minocycline 272
- Conserved dopamine neurotrophic factor for PD 272
- Free radical scavengers for neuroprotection in Parkinson's disease
273
- Antioxidants 273
- Melatonin 273
- Tea extracts as neuroprotectives 273
- Nicotine as a neuroprotective in PD 274
- Gene therapy for PD 274
- Implantation of genetically engineered cells 274
- Gene therapy using GDNF and neurturin 275
- Glutamic acid decarboxylase gene therapy 275
- Parkin gene therapy 276
- Concluding remarks about gene therapy for PD 276
- Heat shock protein 70 277
- Liver X receptor β agonists 277
- Neuroprotective effect of leucine-rich repeat kinase-2 inhibitors
277
- Neuroprotective effect of DJ-1 protein 277
- Neurotrophic factors 277
- Basic fibroblast growth factor for PD 278
- BDNF for PD 278
- GDNF for PD 278
- MANF for PD 279
- Neurturin for PD 279
- Platelet derived growth factor 280
- Clinical trials with NTFs 280
- Nrf2-mediated neuroprotection in PD 280
- Omega-3 polyunsaturated fatty acids 280
- RAB3B overexpression 281
- RNAi therapy for PD 281
- Safinamide 281
- Sirtuin 2 inhibitors for neuroprotection in PD 282
- Statins and PD 282
- Targeting Bax 283
- Vitamin D for neuroprotection in PD 283
- Vaccine for PD 283
- Clinical trials of neuroprotection in Parkinson's disease 284
- Evaluation of neuroprotective therapies for PD 285
- Current status and future challenges for neuroprotection in PD 286
8. Neuroprotection in Alzheimer Disease 289
- Introduction 289
- Pathomechanism of Alzheimer's disease 289
- Role of glutamate transport dysfunction in AD 290
- Role of neurotrophic factors in the pathomechanism of AD 290
- Management of Alzheimer's disease 290
- Neuroprotection in Alzheimer's disease 291
- Inhibition of Aβ formation and aggregation 292
- AN-1792 292
- Cadmium telluride nanoparticles prevent Aβ fibril formation
293
- Clioquinol 293
- Colostrinin 294
- FKBP52 for neuroprotection from Cu toxicity in AD 294
- Monoclonal antibody m266 294
- Phenserine 294
- Secretase inhibitors 295
- Inhibition of neuroinflammation 295
- Etanercept 295
- Neurotrophic factors/ gene therapy 296
- NGF gene therapy 296
- AL-108 297
- Targeting plasminogen activator inhibitor type-1 gene 297
- Estrogen and AD 298
- Antioxidants 298
- NSAIDS 298
- Memantine 298
- Dimebon 299
- Cerebrolysin 300
- Curcumin as a neuroprotectant in Alzheimer disease 300
- Ginko biloba 301
- Tetrahydrocannabinol for neuroprotection in AD 301
- Ladostigil tartrate 302
- Phosphodiesterase inhibitors as neuroprotectives 302
- PPAR-γ agonists 302
- Role of statins in reducing the risk of AD 303
- Combined therapeutic approaches to AD 303
- Clinical trials in AD 303
- Future prospects of neuroprotection in AD 311
- Mild cognitive impairment 311
- Relation of MCI to AD 311
- Neuroprotection in MCI 312
9. Neuroprotection in Huntington Disease 315
- Introduction 315
- Pathophysiology of HD 315
- Management of Huntington's disease 316
- Neuroprotection in Huntington's disease 317
- Antipsychotic D2 and 5-HT1A antagonists 318
- Caspase inhibitors 318
- Clioquinol for HD 318
- Creatine for stabilizing bioenergetic defects 318
- Cysteamine 319
- Drugs that block inappropriate calcium release from neurons 319
- Enhancing protease activity for clearance of mHtt 319
- Eicosapentaenoic acid 319
- Free radical scavengers 320
- Histone deacetylase inhibitors 320
- Inhibitors of polyglutamine aggregation HD 320
- Pridopidine 321
- RRAS signaling pathway inhibition 321
- Simvastatin as a neuroprotective in HD 322
- Single chain Fv antibodies 322
- SIRT1 activators for neuroprotection in HD 322
- SIRT2 inhibitors for neuroprotection in HD 323
- Synaptic activation of NMDA receptors 323
- Targeting mutant huntingtin protein 323
- Tetrabenazine 324
- Combinatorial therapy and targeting multiple pathways in HD 324
- Cell transplants 324
- Neurotrophic factors and gene therapy 325
- RNAi and antisense therapies for Huntington's disease 326
10. Neuroprotection in Amyotrophic Lateral Sclerosis 329
- Introduction 329
- Pathophysiology of ALS 329
- Neuroprotective therapies for ALS 332
- Activated protein C 333
- AEOL 10150 334
- AIMSPRO 334
- Anakinra 334
- Antisense therapy 335
- Arimoclomol for ALS 335
- Ceftriaxone for ALS 335
- Coenzyme Q10 for ALS 336
- COX-2 inhibitors for ALS 336
- Creatine for ALS 336
- Dexpramipexole 337
- Diallyl trisulfide 337
- Erythropoietin for ALS 337
- Gene therapy for ALS 337
- Glatiramer acetate 338
- Insulin-like growth factor 338
- Ketogenic diet for neuroprotection in ALS 339
- Lenalidomide 339
- Lithium for neuroprotection in ALS 340
- Methylcobalamin 340
- Minocycline for ALS 340
- Olesoxime as neuroprotective for ALS 341
- ONO-2506 for ALS 341
- Riluzole 341
- RNAi-based therapy for ALS 341
- Sodium phenylbutyrate 342
- Stem cell therapy 342
- Clinical applications 342
- Stem cell-based drug discovery for ALS 343
- Suppressors of mTDP-43 toxicity 344
- Talampanel 344
- Tamoxifen 344
- Vaccination for ALS caused by SOD1 mutations 344
- Vascular endothelial growth factor for ALS 345
- Vitamin E for ALS 345
- Clinical trials of neuroprotective therapies for ALS 345
- Concluding remarks and future prospects 348
11. Neuroprotection in Miscellaneous Neurological Disorders 349
- Introduction 349
- Age-related dementia 349
- Enhancing endogenous neurotrophic support of the aging brain 349
- Pharmacological approaches for treatment of age-related dementia
350
- Physical exercise to prevent decline of mental function with aging
351
- Vascular dementia 351
- Prediction of dementia in persons with vascular risk factors 351
- Management of subcortical vascular dementia 352
- Dementia with Lewy bodies 353
- Neuroprotection in AIDS dementia 353
- Multiple system atrophy 354
- Epilepsy 354
- Mechanisms of neuronal damage in epilepsy 354
- Strategies for neuroprotection in epilepsy 355
- Control of seizures by AEDs and neuroprotection 356
- Prevention of seizures by ketogenic diet 357
- Cell therapy for neuroprotection in epilepsy 358
- Cell therapy of posttraumatic epilepsy 358
- Cell therapy for temporal lobe epilepsy 358
- Cell therapy for pharmacoresistant epilepsies 359
- Gene therapy for neuroprotection in epilepsy 359
- Spinal and bulbar muscular atrophy 360
- Spinal muscular atrophy 360
- Multiple sclerosis 361
- Introduction 361
- Epidemiology of multiple sclerosis 361
- Pathophysiology 362
- Current management of multiple sclerosis 362
- Specific therapies for MS based on pathomechanism 363
- Neuroprotection in multiple sclerosis 363
- Clinical trials of neuroprotective therapies for MS 364
- Neuroprotection by control of progressive forms of multiple sclerosis
367
- Neuroprotection by controlling autoimmune inflammation in the brain
367
- Neuroprotection by sealing the BBB with imatinib 368
- TRPM4 cation channel blockers 368
- Remyelination for neuroprotection in multiple sclerosis 368
- Agents for neuroprotection in multiple sclerosis 368
- Angiotensin-II inhibitors 368
- Antiglutamate agents 369
- Antioxidants for neuroprotection in MS 369
- Antisense and RNAi approaches to MS 369
- Cell therapy for multiple sclerosis 370
- Cladribine 372
- Curcumin as a neuroprotectant in multiple sclerosis 373
- Dalfampridine in MS 373
- Dimethyl fumarate 373
- DNA vaccine for MS 374
- Erythropoietin as a neuroprotective in MS 374
- Fingolimod (FTY720) 374
- Fusokine composed of GM-CSF and IL-15 for immune suppression 375
- Gene therapy for MS 375
- Ibudilast for MS 376
- IVIG for MS 376
- Kinase inhibitors 376
- Laquinimod 376
- Monoclonal antibodies for MS 377
- Natalizumab 377
- Natural human antibodies for repair of myelin 377
- Neurotrophic factors for multiple sclerosis 378
- Oral immunomodulatory agents for MS 379
- Recombinant T-cell ligands 379
- Statins for MS 379
- Teriflunomide 380
- Concluding remarks and future prospects for neuroprotection in MS
380
- Neuroprotection in transverse myelitis 381
- Neuroprotection in decompression sickness 381
- Neuroprotection in victims of drowning 382
- Neuroprotection in CSF circulatory disorders 382
- Neuroprotection in hydrocephalus 382
- Neuroprotection in normal pressure hydrocephalus 383
- Neuroprotection in infections of the CNS 384
- Neuroprotection in bacterial meningitis 384
- Mechanism of neural injury in bacterial meningitis 384
- Strategies for neuroprotection 384
- Neuroprotection in cryptococcal meningitis 385
- Neuroprotective approach to rabies 385
- Neuroprotection in cerebral malaria 386
- Neuroprotection in hypertensive encephalopathy 386
- Neuroprotection in toxic encephalopathies 386
- Hepatic encephalopathy 387
- Management of hepatic encephalopathy 387
- Encephalopathy due to organophosphorus poisoning 388
- Neuroprotection against chemotherapy-induced brain damage 388
- Neuroprotection against alcohol 389
- Alcoholic neurologic disorders 389
- Fetal alcohol syndrome 389
- Pathogenesis of alcohol-induced damage to the nervous system 389
- Neuroprotection against neurotoxicity of alcohol 390
- Neuroprotection against radiation encephalopathy 390
- Neuroprotection in hypoxia-ischemia 391
- Neuroprotection in neonatal hypoxic-ischemic brain injury 391
- Hyperbaric oxygen for neonatal hypoxia-ischemia 392
- Hypothermia for neonatal hypoxia-ischemia 392
- Minocycline for neonatal hypoxia-ischemia 393
- Nicotinamide mononucleotide adenylyl transferase 1 393
- Nitric oxide inhalation for neonatal hypoxia-ischemia 393
- Plasminogen activator inhibitor-1 for neonatal hypoxia-ischemia
393
- Recombinant erythropoietin for neonatal hypoxia-ischemia 393
- Neuroprotection in carbon monoxide poisoning 394
- Pathomechanism of CO poisoning as a basis for neuroprotection 394
- Management of CO poisoning 395
- Syndrome of delayed post-hypoxic leukoencephalopathy 395
- Neuroprotection of the fetus 396
- Neuroprotection in sleep apnea 396
- Neuroprotection in complications of diabetes 397
- Neuroprotection in hypoglycemic coma 397
- Neuroprotection in diabetic retinopathy 398
- Neuroprotection in mitochondrial dysfunction 399
- Mitochondrial permeability transition 399
- Mitochondrial approaches for neuroprotection 399
- Methylene blue 400
- Role of nanolasers in evaluation of mitochondrial neuroprotectants
401
- Neuroprotection in mitochondrial encephalopathies 401
- Neuroprotection in psychiatric disorders 401
- Cognitive impairment in schizophrenia 401
- Neuroprotection in schizophrenia 402
- Electroconvulsive therapy and neuroprotection 402
- Neuroprotection in hearing loss 403
- Causes of hearing loss 403
- Pathomechanism of hearing loss 404
- Prevention and treatment of hearing loss 404
- Hyperbaric oxygen for hearing loss 404
- Stem cell therapy for hearing loss 405
- Auditory hair cell replacement by gene therapy 405
- Pharmaceutical approaches to hearing loss 406
- Neuroprotection of peripheral nerves 406
- Neuroprotective agents for peripheral nerves 407
- Acetyl-L-carnitine for peripheral nerve injuries 407
- Atorvastatin for peripheral nerve injuries 407
- Erythropoietin for neuroprotection in peripheral nerve injuries
408
- Neuroprotection in peripheral nerve injuries 408
- Role of hyperbaric oxygen in peripheral nerve injuries 408
- Role of neurotrophic factors in peripheral nerve injuries 409
- Pharmacological approaches to Schwann cells 409
- Role of gene therapy in neuroprotection of injured peripheral nerves
409
- Schwann cell transplantation for peripheral nerve injury 409
- Peripheral neuropathy 409
- Neuroprotection in diabetic neuropathy 410
- Cell therapy for neuroprotection in diabetic neuropathy 410
- Gene therapy with zinc finger DNA-binding proteins 410
- Neuroprotection in chemotherapy-induced neuropathy 411
- Chronic inflammatory demyelinating polyradiculoneuropathy 411
- Neuroprotection in CIDP 411
12. Neuroprotection of the Optic nerve and the Retina 414
- Introduction 414
- Neuroprotection in optic neuropathy 414
- Neuroprotection in optic neuritis 415
- Neuroprotection in optic nerve trauma 415
- Potential regeneration of the optic nerve 416
- Subthreshold transpupillary thermotherapy for protection of RGCs
416
- Neuroprotection of optic nerve in glaucoma 416
- Aminoguanidine as a neuroprotective in glaucoma 418
- Antiglutamate agents for neuroprotection of optic nerve 418
- Betaxolol 418
- NGF eye drops 418
- Targeting Aβ in glaucoma treatment 419
- TNF-α blockers for neuroprotection in glaucoma 419
- Concluding remarks about neuroprotection in glaucoma 419
- Neuroprotection in retinal ischemia 419
- Endogenous neuroprotection in the retina 420
- β-adrenoceptor antagonists 420
- Brimonidine as a neuroprotective is ischemic retinopathy 421
- Thioredoxin as a neuroprotective agent in retinal ischemia 421
- Erythropoietin for neuroprotection of retinal ischemia 421
- Gene therapy for retinal neuroprotection 422
- Hyperbaric oxygen for central retinal artery occlusion 422
- Protection against oxygen-induced retinopathy 422
- Neuroprotection in macular degeneration 423
- Epidemiology 423
- Pathomechanism of AMD 423
- Current treatment of AMD 423
- Novel neuroprotective strategies against retinal degeneration 424
- Antiangiogenic agents 425
- Humanized MAb against Aβ 426
- LXR agonists 426
- Protection of retinal cells from oxidative-stress-induced apoptosis
426
- Neurotrophic factors for neuroprotection in AMD 427
- CNTF for neuroprotection in AMD 427
- N-acetylserotonin derivatives 427
- Nutritional protection against AMD 427
- Progestogenic hormones 428
- Tandospirone 428
- Cell therapy for macular degeneration 428
- Retinal pigment epithelial cells 428
- Stem cells 428
- Neural progenitor cells 429
- Gene therapy for retinal degeneration 429
- RNAi-based treatments for AMD 429
- Neuroprotection in proliferative diabetic retinopathy 430
- RNAi-based approaches to diabetic retinopathy 430
- Clinical trials for optic nerve and retinal neuroprotection 431
13. Neuroprotection during Anesthesia and Surgery 433
- Introduction 433
- Anesthetic agents as neuroprotectives 433
- Barbiturates 433
- Thiopental 434
- Etomidate 435
- Propofol 435
- Ketamine 435
- Gaseous anesthetics 436
- Isoflurane 436
- Xenon 436
- Local anesthetics 437
- Monitoring of CNS function during anesthesia and surgery 437
- Monitoring of cerebral function 437
- Monitoring of spinal cord function during spinal surgery 437
- Neuroprotection during cardiovascular procedures 438
- CNS complications of cardiac surgery 438
- Neuroprotective strategies during cardiac surgery 439
- Neuroprotection during coronary artery bypass grafting 441
- Neuroprotection before anticipated or induced cardiac arrest 441
- Spinal cord protection during cardiovascular surgery 442
- Cerebral protection during organ transplantation surgery 442
- Cerebral protection during neurosurgery 442
- Cerebral angiography and endovascular surgery 443
- Cerebral protection during surgery for arteriovenous malformations
443
- Cerebral protection during surgery of intracranial aneurysms 443
- Management of subarachnoid hemorrhage 444
- Vasospasm associated with subarachnoid hemorrhage 444
- Cerebral protection during carotid endarterectomy 446
- Cerebral protection during surgery of brain tumors 446
- Neuroprotective measures prior to surgery 447
- Neuroprotection following surgery 447
14. Markets for Neuroprotective Therapies 449
- Introduction 449
- The financial burden of CNS damage 449
- Markets for neuroprotective therapies 449
- Markets according to therapeutic areas 449
- Stroke 450
- CNS injury 450
- Alzheimer disease 451
- Parkinson disease 451
- Multiple sclerosis 451
- Epilepsy 451
- Values of neuroprotective therapies in major world markets 451
- Unmet needs in neuroprotectives 452
- Future prospects of neuroprotective therapies 453
- Challenges in neuroprotective drug development 453
- Promising areas of research in neuroprotection 454
- Autoreactive antibodies 454
- Biological therapies for neuroprotection 454
- Multidisciplinary approaches to neuroprotection 455
15. References 457
Tables
- Table 1-1: Historical landmarks in the development of neuroprotection
29
- Table 1-2: Intrinsic neuroprotective factors 30
- Table 1-3: Common features of pathophysiology of brain damage in diseases
37
- Table 1-4: Place of neuroprotection in management of CNS disorders
39
- Table 1-5: Indications for the use of neuroprotection 39
- Table 2-1: A classification of neuroprotective agents 47
- Table 2-2: The neuroprotective effect of antiepileptic drugs
56
- Table 2-3: Neuroprotective affect of minocycline in animal models
60
- Table 2-4: Classification of antioxidants or free radical scavengers with
neuroprotective potential 68
- Table 2-5: Role of erythropoietin in the nervous system 73
- Table 2-6: Ionotropic glutamate receptors 78
- Table 2-7: Classification of metabotropic glutamate receptors (mGluRs)
79
- Table 2-8: Methods for neuroprotection based on nonpharmacological
preconditioning 127
- Table 3-1: Cerebrovascular diseases that are relevant to neuroprotection
131
- Table 3-2: Neuroprotective strategies for stroke 140
- Table 3-3: Neuroprotective gene transfer in models of cerebral ischemia
172
- Table 3-4: Neuroprotective gene therapy in animal stroke models
172
- Table 3-5: Neuroprotective agents in clinical development for acute
cerebrovascular disease 174
- Table 3-6: Some failed trials for neuroprotective therapy for stroke
178
- Table 3-7: Preclinical assessment of neuroprotective agents in acute
stroke models 187
- Table 4-1: Current conventional management of traumatic brain injury
197
- Table 4-2: Neuroprotective strategies for traumatic brain injury
199
- Table 4-3: Ongoing or completed clinical trials for neuroprotection in TBI
215
- Table 4-4: Discontinued or failed clinical trials for neuroprotection in
TBI 216
- Table 5-1: Secondary mechanisms in spinal cord injury 223
- Table 5-2: Neuroprotective and regenerative approaches for SCI
224
- Table 5-3: Clinical trials for neuroprotection in SCI 238
- Table 6-1: Neurodegenerative disorders with dementia 247
- Table 6-2: Glutamate-based therapies in clinical development for
neurodegenerative disorders 253
- Table 7-1: Prevalence of Parkinson's disease in major markets 2012-2022
255
- Table 7-2: Factors in the etiology of Parkinson's disease 255
- Table 7-3: Strategies for the treatment of Parkinson's disease
262
- Table 7-4: Current clinical trials of neuroprotective therapies for
Parkinson disease 284
- Table 7-5: Failed clinical trials of neuroprotective therapies for
Parkinson disease 284
- Table 7-6: Evaluation of neuroprotective agents for PD 286
- Table 8-1: Cholinergic approaches to the treatment of Alzheimer's disease
291
- Table 8-2: Neuroprotective agents for Alzheimer's disease 291
- Table 8-3: Clinical trials for neuroprotection in Alzheimer disease
304
- Table 8-4: Discontinued, failed or inconclusive clinical trials of
Alzheimer disease 308
- Table 8-5: Strategies for discovery of neuroprotective therapies for AD
311
- Table 9-1: Neuroprotective approaches in HD 317
- Table 10-1: Hypotheses for the pathogenesis of amyotrophic lateral
sclerosis 329
- Table 10-2: Classification of neuroprotective agents for amyotrophic
lateral sclerosis 332
- Table 10-3: Clinical trials of neuroprotective therapies for ALS
345
- Table 10-4: Failed or discontinued trials of neuroprotective therapies for
ALS 347
- Table 11-1: Therapeutic approaches to subcortical vascular dementia
352
- Table 11-2: Pharmacological neuroprotection against the sequelae of
seizures 356
- Table 11-3: Neuroprotective effect of AEDs in animal models of status
epilepticus (SE) 357
- Table 11-4: Specific therapies for MS based on postulated pathomechanisms
363
- Table 11-5: Approved neuroprotective therapies for multiple sclerosis
364
- Table 11-6: Neuroprotective therapies for multiple sclerosis in clinical
trials 365
- Table 11-7: Failed or discontinued trials of neuroprotective therapies for
ALS 365
- Table 11-8: Approaches to neuroprotection in neonatal hypoxia-ischemia
392
- Table 11-9: Drugs with neuroprotective effect at mitochondrial level
400
- Table 11-10: Causes of sensorineural hearing impairment 403
- Table 11-11: Strategies for prevention and treatment of sensorineural
hearing loss 404
- Table 11-12: Agents for neuroprotection of the peripheral nervous system
407
- Table 12-1: Causes of optic neuropathy 414
- Table 12-2: Neuroprotection of the optic nerve in glaucoma 417
- Table 12-3: Strategies for neuroprotection in retinal ischemia
420
- Table 12-4: Novel neuroprotective strategies against retinal degeneration
424
- Table 12-5: Clinical trials for optic nerve and retinal neuroprotection
431
- Table 13-1: CNS complications associated with cardiac procedures
438
- Table 13-2: Strategies for protection of the brain during cardiac surgery
440
- Table 13-3: Medical and surgical methods of cerebral vasospasm management
445
- Table 13-4: Neuroprotection by prevention of vasospasm 445
- Table 14-1: Neuroprotective market values 2012-2022 450
- Table 14-2: Values of neuroprotective therapies in major world markets
from 2012-22 451
- Figures
- Figure 2-1: Mechanism of neuroprotective effect of sigma-1 receptor
agonists 55
- Figure 2-2: NMDA receptor ion channel complex 83
- Figure 2-3: Neuroprotective effect of galantamine 105
- Figure 3-1: Some steps in the ischemic cascade and site of action of
neuroprotectives 132
- Figure 3-2: A roadmap for neuroprotection 188
- Figure 4-1: Cascade of events following traumatic brain injury
192
- Figure 5-1: Pathomechanism of acute spinal cord injury 222
- Figure 7-1: Neuroprotective strategies against death of
dopamine-containing neurons in PD 261
- Figure 9-1: Role of HTT protein in pathogenesis of HD and points of
intervention 323
- Figure 9-2: Antisense therapeutic approaches to HD for lowering huntingtin
327
- Figure 11-1: Common mechanisms of neural damage in cerebral ischemia and
seizures 355
- Figure 11-2: Role of neuroprotection in epilepsy and its treatment
356
- Figure 14-1: Unmet therapeutic needs in neuroprotective therapies
453
PartII
16. Companies Developing Neuroprotective Therapies 5
- Introduction 5
- Profiles of companies 5
- Collaborations 152
Tables
- Table 16-1: Neuroprotectives in development by AstraZeneca 22
- Table 16-2: Collaborations of companies in the area of neuroprotection
152
Neuroprotection - Drugs, Markets and Companies published by Jain Pharmabiotech in April 1, 2013. This report price starts from US $ 5000.
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