NEW YORK, Nov. 30, 2011 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
Neuroprotection - Drugs, Markets and Companies
http://www.reportlinker.com/p0203546/Neuroprotection---Drugs-Markets-and-Companies.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Drug_and_Medication
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 a profile of 130 companies that have a neuroprotective product or products along with 110 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 65 tables and 11 figures.
Market analysis of currently used productsthat have a neuroprotective effect are analyzed for the year 2010. 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 2015 when it will constitute a major and important component of the CNS market. Forecasts are made until 2020. 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
0. Executive Summary 23
1. Introduction 27
Definitions 27
Historical development of neuroprotection 27
Intrinsic neuroprotective factors 28
Neuroprotective gene expression 29
Upregulation of GADD34 29
Induction of NR4A proteins by CREB in neurons 30
Neurotrophic factors 30
Intrinsic nonenzymatic antioxidants 30
Activation of transcription factor Nrf2 31
Intrinsic neuroprotective proteins 31
?B-crystallin 31
Excitatory amino acid transporters 31
Extracellular serine protease thrombin 31
Galanin 32
Neuroglobin 32
Nuclear factor I-A 32
Prion protein 33
Rai adaptor protein 33
Stem cell factor 33
Role of the immune system in neuroprotection 34
Induction of DNA repair enzymes for neuroprotection 34
Pathomechanisms of CNS injury as basis for neuroprotection 35
Biomarkers of neurological disorders and neuroprotection 35
CNS biomarker identification using proteomics 35
Brain imaging for detection of biomarkers 36
Role of neuroprotection in various neurological disorders 36
Neuroprotection and neuroregeneration 37
Acute versus chronic neuroprotection 37
Discovery and evaluation of neuroprotective agents 38
Neuroprotective drug discovery 38
Discovery of CNS drugs that penetrate the blood-brain barrier 39
In vitro assays for the evaluation of neuroprotective agents 39
Oxidative injury model to test neuroprotective drugs 39
Apoptosis model for designing neuroprotective drugs 40
Transgenic mouse models of neurological disorders 40
Evaluating effects of neuroprotective drugs on living brain slices 40
Role of brain imaging in neuroprotective drug discovery and development 41
Positron emission tomography 41
Role of single photon emission computed tomography 41
Functional CT scanning to evaluate cerebrovascular protection 42
Magnetic resonance imaging for the evaluation of neuroprotectives 42
Application of nanotechnology to neuroprotection 43
Evaluation criteria for potential neuroprotective agents 43
2. Neuroprotective Agents 45
Classification of neuroprotective agents 45
Activated protein C 49
Activity-dependent neuroprotective protein 49
Adenosine analogs 50
Propentofylline 50
Antidepressants 51
Antidepressant-induced neurogenesis 51
Neurogenesis induced by electroconvulsive therapy 51
Neuroprotective effect of selective serotonin reuptake inhibitors 51
Antiepileptic drugs as neuroprotectives 53
Phenytoin 54
Valproic acid 54
Levetiracetam 54
Antiinflammatory agents 55
Aspirin 55
Interleukin-1 antagonists 55
COX-2 inhibitors 56
Nimesulide 56
Gold microparticles as anti-neuroinflammatory agents 56
Minocycline 57
Anti-apoptosis agents 58
Activated protein C 58
Calpain inhibitors 59
Caspase inhibitors 59
DNA binding drugs 59
Lithium 59
Olesoxime 60
Omega-3 fatty acids 60
Docosahexaenoic acid 60
Poly(ADP-ribose) polymerase inhibitors 61
Prevention of apoptosis by binding of proNGF to sortilin 61
Antioxidants/free radical scavengers 62
Free radical generation 62
Natural defenses against oxidative stress 62
Effects of oxidative damage 62
Oxidative damage and aging 62
Neuronal damage by free radicals 63
Oxidative damage and neurodegenerative disorders 63
Measures to control oxidative stress 64
Categories of therapeutic antioxidants 64
Alpha-phenyl-tert-butylnitrone 64
Coenzyme Q10 65
Dihydroergocryptine 65
Flavonoids 66
Mitochondria-targeted antioxidants 66
Nanoparticles as neuroprotective antioxidants 66
Neuroleptics as antioxidants 67
Nitrones 67
Translation of antioxidant neuroprotection from preclinical to clinical 68
Carbon monoxide and heme oxygenase 68
Cell transplants 68
Cells secreting neuroprotective substances 68
Stem cells 69
Stem cell activation for neuroprotection/regeneration by glucocorticoids 69
Cytokines 69
Erythropoietin 69
Non-erythropoietic EPO variants and mimics 71
Granulocyte colony-stimulating factor 72
Delta-opioid receptor agonists 72
FK960 72
Gene therapy 73
Glucagon-like peptide 74
Glatiramer acetate 74
Glutamate antagonists 74
Neuroprotection by scavenging blood glutamate 75
N-acylethanolamines for protection against glutamatergic excitotoxicity 76
Glutamate transporters 76
Glutamate transporter-mediated neuroprotective effect of drugs 76
Neuroprotection by targeting KAI subunit of kainate receptor 77
Glycine-proline-glutamate analogs 77
Herbal preparations 77
Flavonoid wogonin 78
Ginseng 78
Hydrogen sulfide 78
NMDA receptor ion channel complex 79
NMDA receptor antagonists 80
NMDA NR2B subunit receptor antagonists 80
Ifenprodil 80
Memantine as a neuroprotective agent 80
Magnesium 81
NAALADase inhibitors 81
Gacyclidine 81
N-alkylglycines 81
AMPA receptor modulators 82
Metabotropic glutamate receptor modulators 82
Cannabinoids 83
Dexanabinol 83
Glutathione 84
Heat shock proteins 84
Hormones 85
Estrogen and neuroprotection 85
Neuroprotective effect of estrogen receptor ligands 85
Selective estrogen receptor modulators 86
Mitochondrial mechanisms of estrogen neuroprotection 86
Insulin 87
Ion Channel modulators 87
Calcium channel blockers. 87
Ziconotide 88
Na+ channel blockers. 88
Neuroprotective potassium channel inhibitors 89
Kynurenine inhibitors 89
Leukocyte adhesion inhibitors 89
Modafinil 90
Neural regeneration protein 90
Neurite outgrowth-promoting prostaglandin compounds 91
Neuroimmunophilins 91
Cyclosporin-A 91
FK506 92
Rapamycin 92
Neurotrophic factors 93
Activity-dependent neurotrophic factor 93
Bone morphogenetic proteins 93
Brain-derived neurotrophic factor 94
Ciliary neurotrophic factor 94
Fibroblast growth factors 95
Glial cell line-derived neurotrophic factor 95
Insulin-like growth factor 96
Nerve growth factor 96
Neurotrophins 97
Osteogenic protein-1 97
Pigment epithelium-derived factor 97
Transforming growth factor-?1 98
Vascular endothelial growth factor 98
Neurotrophic factor-related neuroprotective agents 98
Amitriptyline as a TrkA and TrkB receptor agonist 98
Colivelin 98
Gambogic amide 99
Inosine 99
Meteorin 99
Oxygen-regulated protein 150 kD 100
Prosaptide 100
Siagoside 100
Small molecule activators of the Trk receptors 100
Nicotine and nicotinic receptor agonists 101
Neuroprotective effect of galantamine mediated via ?7nAChRs 101
Galantamine-induced A? clearance via ?7nAChRs 102
Nitric oxide-based neuroprotection 102
Nitric oxide synthase inhibitors 102
Nitric oxide mimetics 103
Nootropics 103
Piracetam 104
Nutraceuticals and food constituents 104
Coffee 104
Creatine 105
Curcumin/curry 105
Curcumin as a neuroprotectant in Alzheimer disease 105
Curcumin as a neuroprotectant in stroke 105
Curcumin as a neuroprotectant in multiple sclerosis 106
Mechanism of neuroprotective effect of curcumin 106
Glyceryltriacetate 106
Green tea 106
Nicotinamide 107
Resveratrol 107
Osmotic diuretics 108
Mannitol 108
Osteopontin 108
Oxygen therapeutics 109
Oxygen carriers 109
Hemoglobin-based oxygen carriers 109
Perfluorocarbons as oxygen carriers 110
Hyperbaric oxygen therapy 111
Peptides 111
C3-derived peptide for neuroprotection and neuroregeneration 111
Corticotropin-releasing hormone 111
Thyrotropin-releasing hormone 112
Vasoactive intestinal peptide 112
Pharmacological preconditioning 113
PPARs as drug targets for neuroprotection 113
Riluzole 113
Role of RNA interference in neuroprotection 114
Sigma receptor agonists as neuroprotective agents 114
SIRT group of proteins 114
Statins 115
Steroids 116
Dehydroepiandrosterone 116
HF0220 117
Sulforaphane 117
Tauroursodeoxycholic acid 117
Tetanus toxin as a neuroprotective agent 118
Thrombolytic agents as neuroprotective agents 118
Uncoupling protein 2 118
Vaccines as neuroprotectives 119
Vitamins as neuroprotective agents 119
Vitamin B12 119
Vitamin D 120
Non-pharmacological approaches to neuroprotection 120
Environmental enrichment 120
Mental training 120
Physical exercise 120
Hypothermia 121
Limitations of hypothermia 121
Hypothermic neuroprotection in hypoxia-ischemia 122
Hibernation induced by hydrogen sulfide 122
Ketogenic diet 122
Nonpharmacological preconditioning for neuroprotection 123
Transcranial magnetic stimulation 124
Electrical fields for improvement of cerebral function in neurodegeneration 124
Neuroprotective effect of exercise 125
Hibernation and neuroprotection 125
Suspended animation and neuroprotection 126
3. Neuroprotection in Cerebrovascular Disease 127
Introduction 127
Pathophysiology of cerebral ischemia 127
Calcium overload 128
Ion channel dysfunction in stroke 128
Role of oxygen free radicals in cerebral ischemia 129
Role of nitric oxide in cerebral ischemia 129
Glutamate as a biomarker of stroke 129
Cerebral edema in stroke 129
Gene expression in response to cerebral ischemia 130
Induction of heat shock proteins in stroke 130
Role of cytokines and adhesion molecules in stroke 130
Tumor necrosis factor-? 130
Interleukin-1 and IL-6 131
Adhesion molecules 131
DNA damage and repair in cerebral ischemia 131
Role of neurotrophic factors in stroke 132
Problems requiring investigation of the role of NTFs in stroke 132
Role of Poly(ADP-ribose) polymerase (PARP) gene 132
Role of protease-activated receptor 1 133
Reperfusion injury after cerebral ischemia 133
Neuroprotection according to zones in cerebral infarction 133
Zone of ischemic infarction 133
Penumbra 134
Current management of stroke 134
Neuroprotection in stenosis of intracranial arteries 135
Neuroprotection in transient ischemic attacks 135
Neuroprotective therapies for stroke 135
?B-crystallin as a neuroprotectant in stroke 136
Acid-sensing ion channel blockers 137
AMPA receptor antagonists as neuroprotectives for stroke 137
Zonampanel 137
Antiapoptotic neuroprotectives 137
NIM811 137
Creatine as neuroprotective in stroke 138
Lithium as a neuroprotective in stroke 138
TUDCA as a neuroprotective in stroke 138
Coagulation inhibitors as neuroprotectives 138
Heparin and enoxaparin 139
Warfarin vs dabigatran 139
Apixaban 139
Antiepileptic drugs as neuroprotectives in stroke 140
Tiagabine 140
Topiramate 140
Zonisamide 140
Anti-HMGB1 monoclonal antibody 140
Antioxidant approaches 141
Carnosine as a neuroprotective in stroke 141
Dehydroascorbic acid 141
Tocotrienols 142
Uric acid 143
Antiglutamate compounds 143
MRZ 2/576 143
L-Phenylalanine 143
Arimoclomol for stroke 143
Cardiac glycosides as neuroprotectives in stroke 144
Clenbuterol 144
Cox-2 inhibitors for ischemic stroke 144
Docosahexaenoic acid for ischemic stroke 144
Estrogen for stroke 145
Extendin-4 146
Flavones for neuroprotection in stroke 146
Granulocyte-macrophage colony-stimulating factor for cerebral ischemia 147
Modulation of histamine H2-receptors 147
Inosine for stroke 147
Insulin-like growth factor-I 148
Intravenous immunoglobulin as neuroprotective in stroke 148
Ischemic preconditioning for neuroprotection in stroke 148
Ketone bodies for neuroprotection in stroke 149
Mineralocorticoid receptor blockade for neuroprotection 149
Multifunctional neuroprotective agents 149
Nasal delivery of neuroprotective agents in stroke 150
Neuroserpin as a neuroprotective in stroke 150
N-2-mercaptopropionyl glycine 150
NeuroAid 151
Neurotrophic factors as neuroprotectives for stroke 151
AX200 151
Brain-derived neurotrophic factor 151
Fibroblast growth factor 152
Glial cell line-derived neurotrophic factor 152
Insulin-like growth factor-1 152
Neuregulin-1 153
NO-based strategies for neuroprotection in cerebral ischemia 153
Perlecan domain V 154
Peroxisome proliferator-activated receptor-? agonists 154
PGE2 EP2 receptor activation 154
Pioglitazone for reduction of stroke risk in diabetes 154
Progesterone 154
Proteosome inhibitors 155
Statins for prevention and neuroprotection in stroke 155
Sildenafil 156
Src receptor blockade 156
Stroke vaccine 156
SUN N4057 157
Thrombosis inhibitors 157
Aspirin 157
Clopidogrel 157
Dipyridamole 158
Vitamin E for neuroprotection in stroke 158
Neuroprotection in reperfusion injury 158
Prevention of hemorrhage following ischemic stroke 159
Non-pharmacological neuroprotective therapies for stroke 159
Preconditioning for neuroprotection against cerebral ischemia 159
Hypothermia for neuroprotection in acute stroke 160
Hyperbaric oxygen therapy for neuroprotection in acute stroke 160
Infrared laser therapy for ischemic stroke 161
Neurostimulation of sphenopalatine ganglion 162
Neurosurgical procedures for neuroprotection in stroke 162
Neurorehabilitation in relation to neuroprotection in stroke 163
Cell therapy for stroke 163
Stem cell transplant for stroke 163
Immortalized cell grafts for stroke 164
Stimulation of instrinsic stem cells for repair of brain in stroke 164
Neuroprotective vaccines for stroke 165
Gene therapy for neuroprotection in cerebrovascular disease 165
Regulation of microRNAs for neuroprotection in cerebral ischemia 167
RNAi-based therapy for neuroprotection in stroke 167
Neuroprotective therapies for cerebral ischemia: clinical trials 167
Albumin 168
Free radical scavengers 169
DP-b99 170
Minocycline for neuroprotection in stroke 170
Perindopril 171
Failed clinical trials of neuroprotection in stroke 171
Ancrod 172
Aptiganel 173
Cerovive 173
Citicoline 174
Desmoteplase 175
Erythropoietin as a neuroprotective in stroke 176
SPD 502 176
Tirilazad mesylate 176
Selfotel 176
Lubeluzole 177
Nalmefene 177
Gavestinel 177
Nimodipine 177
Sipatrigine 178
Causes of failure of stroke trials 178
Measures for prevention of failures in stroke trials 180
Design of acute stroke trial to facilitate drug approval 181
The ideal neuroprotective agent for stroke 181
Future prospects for neuroprotection in stroke 182
4. Neuroprotection in Traumatic Brain Injury 185
Introduction 185
Cerebral hypoxia/ischemia as a complication of trauma 185
Epidemiology of TBI 185
TBI in the military 185
Pathophysiology of TBI 186
Immediate damage following TBI 187
Cerebral edema following TBI 187
Delayed damage following TBI 187
Mechanism of axonal damage after TBI 187
Role of neuroinflammation in TBI 187
Molecular events following TBI 188
BBB damage after TBI 188
Chronic traumatic encephalopathy 188
Neurocognitive sequelae of TBI 189
Changes in neurotrophic factors following TBI 190
Changes in neurotransmitters following TBI 190
Proteomics of TBI 190
Genetic influences on outcome following TBI 191
Management of TBI 191
Control of intracranial pressure and cerebral edema 192
Corticosteroids 192
Neuroprotection in TBI 193
Antiepileptic drugs for prevention of seizures and neuroprotection 194
Antioxidants 194
Barbiturates 194
?- and ?-secretase inhibitors 195
Beta blockers 195
Bradykinin B2 antagonists 195
Cell cycle inhibitors for TBI 196
COX-2 inhibitors for neuroprotection in TBI 196
Cyclosporin for neuroprotection in TBI 196
Dexanabinol for TBI 197
Erythropoietin for neuroprotection in TBI 197
Gold implants for neuroprotection in focal TBI 197
KN 38-7271 197
Levosimendan 198
Magnesium sulfate 198
Minocycline for TBI 198
Nutritional approaches to neuroprotection in TBI 198
Branched chain amino acids to ameliorate cognitive impairment in TBI 199
Creatine for neuroprotection in TBI 199
Nicotinamide for neuroprotection in TBI 200
Omega 3 fatty acids as neuroprotectives in TBI 200
Neurotrophic factors for TBI 200
Neurosteroids as neuroprotective agents for TBI 201
NMDA receptor antagonists 202
NP-1 202
Nogo-A inhibitor 203
Oxygen carriers for TBI 203
Polyethylene glycol for neuroprotection in TBI 204
Propofol for neuroprotection in TBI 204
Rapamycin as neuroprotective in TBI 204
Simvastatin as neuroprotective in TBI 204
Thyrotropin-releasing hormone analogs 205
Traxoprodil 205
Biological approaches to neuroprotection in TBI 205
Antisense approaches to TBI 205
Cell therapy for TBI 206
Gene therapy for TBI 206
Vaccines for TBI 206
Non-pharmaceutical approaches to neuroprotection in TBI 207
Hyperbaric oxygen therapy for TBI 207
Hypothermia 207
Reduction of microglial migration after TBI 207
Deep brain stimulation for TBI 207
Prophylactic neuroprotection against TBI 208
Role of helmets in protection against TBI 208
Role of physical exercise in protection against TBI 208
Clinical trials of neuroprotective agents in TBI 209
Ongoing clinical trials in TBI 209
Failed clinical trials in TBI 210
Differences between clinical trials and studies in animal models of TBI 211
Subgroup analysis 211
Improving the clinical trial design 211
Clinical trials combining multiple treatment strategies 212
Shortening the trial time 212
Conclusions and future prospects of neuroprotection in TBI 212
5. Neuroprotection in Spinal Cord Injury 215
Introduction 215
Pathophysiology of SCI 215
Secondary mechanisms of SCI 216
Neurotrophic factor changes in SCI 217
Management of SCI 218
Pharmacological neuroprotective agents for SCI 219
4-aminopyridine 219
Antibodies as neurite growth inhibitors in SCI 219
Bacterial enzyme chondroitinase ABC 219
Docosahexaenoic acid as neuroprotective in SCI 220
Erythropoietin as a neuroprotective in SCI 220
Free radical scavengers for neuroprotection in SCI 220
Gacyclidine 221
GYKI 52466 221
Immunosuppressants as neuroprotectants in SCI 221
Interleukin-10 for neuroprotection in SCI 221
Matrix metalloproteinase inhibitors for SCI 222
Methylprednisolone 222
Minocycline as neuroprotective in SCI 222
Neurotrophic factors for neuroprotection after SCI 223
Promotion of regeneration of neurons in SCI 223
Rho pathway and Rho antagonists in SCI 224
Selenium as a neuroprotective for SCI 224
Sialidase for enhancing recovery after SCI 224
Targeting the inflammatory response for neuroprotection in SCI 225
Uric acid as neuroprotective in SCI 225
Non-pharmacological approaches to SCI 225
Hyperbaric oxygen therapy 225
Hypothermia for SCI 225
Cell therapy for SCI 226
Autoimmune T cells against CNS myelin-associated peptide 226
Fetal neural grafts for SCI 226
Olfactory-ensheathing cells for SCI 226
Oligodendrocyte precursor cells for treatment of SCI 227
Schwann cell transplants for SCI 227
Transplantation of glial cells for SCI 227
Stem cells for SCI 227
Bone marrow stem cells for SCI 227
Embryonic stem cells for SCI 228
Transplantation of induced pluripotent stem cells in SCI 228
Transplantation of MSCs for SCI 229
Transplantation of NSCs for SCI 229
Transdifferentiation of stem cells into cholinergic neurons for SCI 230
Gene therapy for SCI 230
Combined approaches to spinal cord injury 231
Discovery of new targets for neuroprotective therapies in SCI 231
Clinical trials in SCI 232
6. Neuroprotection in Neurodegenerative Disorders 233
Introduction 233
Pathomechanism of neurodegeneration 233
Dual role of ?-synuclein in neuroprotection and neurodegeneration 233
Lack of neurotrophic factors 234
Neuroinflammation in neurodegenerative disorders 234
Neurodegeneration associated with protein misfolding 234
Modulation of neurodegeneration by molecular chaperones 234
Intrabodies targeting protein misfolding in neurodegeneration 235
Targeting proteins aggregation to prevent amyloid formation 235
Tau and neurodegeneration 235
TDP-43 proteinopathy and neurodegenerative diseases 236
Role of apoptosis in neurodegenerative disorders 236
Role of glia in neurodegeneration 236
Role of metals in neurodegeneration 237
Viral infections and neurodegeneration 237
AIDS and the nervous system 237
Avian influenza as cause of neurodegeneration 238
Genetic disorders with neurodegeneration 239
Batten disease 239
Friedrich ataxia 240
Pathomechanism of FA 240
Neuroprotection in FA240
Niemann-Pick type C disease 240
Creutzfeldt-Jakob disease 241
Approaches to neuroprotection in neurodegenerative disorders 242
Glutamate-based therapies for neurodegenerative disorders 242
Mitochondria permeability transition pore complex and neuroprotection 243
7. Neuroprotection in Parkinson Disease 245
Introduction 245
Epidemiology of Parkinson's disease 245
Pathophysiology of Parkinson's disease 245
Oxidative stress 246
Excitotoxicity 247
Asynchronous neuronal activity 247
Apoptosis 247
Role of neurotrophic factors 247
Role of misfolding proteins 247
Genetic factors in PD 248
Alteration of dopamine homeostasis 249
Neuroprotective strategies for PD based on pathomechanism 249
RNAi screening to identify neuroprotective genes in a PD model 250
Management of Parkinson's disease 251
Limitation of conventionally administered dopamine therapy 252
Treatment of dementia associated with PD 253
Neuroprotective therapy in PD 253
Neuroprotective effect of currently used drugs for PD 253
Pramipexole 253
Rasagiline mesylate 254
Ropinirole 255
Selegiline 255
Non-pharmacological strategies for neuroprotection in PD 256
Effect of exercise and environmental enrichment on PD 256
Low-calorie diet in PD 256
Development of neuroprotective therapies for PD 257
9-methyl-?-carboline 257
Adenosine AA2 receptor antagonists 257
Antiapoptotic strategies for PD 258
Calcium channel blockers for PD 258
Cell therapies for PD 258
Stem cells for PD 258
Activation of endogenous stem cells and neural precursors 259
Cogane 260
Creatine and minocycline 260
Conserved dopamine neurotrophic factor for PD 260
Free radical scavengers for neuroprotection in Parkinson's disease 261
Antioxidants 261
Melatonin 261
Tea extracts as neuroprotectives 261
Nicotine as a neuroprotective in PD 261
Gene therapy for PD 262
Implantation of genetically engineered cells 262
Gene therapy using GDNF and neurturin 263
Glutamic acid decarboxylase gene therapy 263
Parkin gene therapy 263
Concluding remarks about gene therapy for PD 264
Heat shock protein 70 264
Neuroprotective effect of leucine-rich repeat kinase-2 inhibitors 265
Neuroprotective effect of DJ-1 protein 265
Neurotrophic factors 265
GDNF for PD 265
Neurturin for PD 266
BDNF for PD 266
Basic fibroblast growth factor for PD 266
Platelet derived growth factor 267
Clinical trials with NTFs 267
Nrf2-mediated neuroprotection in PD 267
Omega-3 polyunsaturated fatty acids 267
RAB3B overexpression 268
RNAi therapy for PD 268
Safinamide 268
Sirtuin 2 inhibitors for neuroprotection in PD 269
Statins and PD 269
Targeting Bax 270
Vitamin D for neuroprotection in PD 270
Vaccine for PD 270
Clinical trials of neuroprotection in Parkinson's disease 271
Evaluation of neuroprotective therapies for PD 272
Current status and future challenges for neuroprotection in PD 274
8. Neuroprotection in Alzheimer Disease 275
Introduction 275
Pathomechanism of Alzheimer's disease 275
Role of glutamate transport dysfunction in AD 276
Role of neurotrophic factors in the pathomechanism of AD 276
Management of Alzheimer's disease 276
Neuroprotection in Alzheimer's disease 277
Inhibition of A? formation and aggregation 278
AN-1792 278
Cadmium telluride nanoparticles prevent A? fibril formation 279
Clioquinol 279
Colostrinin 280
FKBP52 for neuroprotection from Cu toxicity in AD 280
Monoclonal antibody m266 280
Phenserine 280
Secretase inhibitors 281
Inhibition of neuroinflammation 281
Etanercept 281
Neurotrophic factors/ gene therapy 282
NGF gene therapy 282
AL-108 283
Targeting plasminogen activator inhibitor type-1 gene 283
Estrogen and AD 284
Antioxidants 284
NSAIDS 284
Memantine 284
Dimebon 285
Cerebrolysin 286
Ginko biloba 286
Tetrahydrocannabinol for neuroprotection in AD 287
Ladostigil tartrate 288
Phosphodiesterase inhibitors as neuroprotectives 288
PPAR-? agonists 288
Role of statins in reducing the risk of AD 288
Combined therapeutic approaches to AD 289
Clinical trials in AD 289
Future prospects of neuroprotection in AD 296
Mild cognitive impairment 296
Relation of MCI to AD 297
Neuroprotection in MCI 297
9. Neuroprotection in Huntington Disease 299
Introduction 299
Pathophysiology of HD 299
Management of Huntington's disease 300
Neuroprotection in Huntington's disease 301
Antipsychotic D2 and 5-HT1A antagonists 302
Caspase inhibitors 302
Clioquinol for HD 302
Creatine for stabilizing bioenergetic defects 302
Cysteamine 303
Drugs that block inappropriate calcium release from neurons 303
Enhancing protease activity for clearance of mHtt 303
Eicosapentaenoic acid 303
Free radical scavengers 304
Histone deacetylase inhibitors 304
Inhibitors of polyglutamine aggregation HD 304
Pridopidine 305
Simvastatin as a neuroprotective in HD 305
Single chain Fv antibodies 306
SIRT2 inhibitors for neuroprotection in HD 306
Synaptic activation of NMDA receptors 306
Tetrabenazine 306
Combinatorial therapy and targeting multiple pathways in HD 307
Cell transplants 307
Neurotrophic factors and gene therapy 308
RNAi therapy for Huntington's disease 308
10. Neuroprotection in Amyotrophic Lateral Sclerosis 311
Introduction 311
Pathophysiology of ALS 311
Neuroprotective therapies for ALS 313
Activated protein C 314
AEOL 10150 315
AIMSPRO 315
Anakinra 315
Arimoclomol for ALS 316
Antisense therapy 316
Creatine for ALS 316
Ceftriaxone for ALS 316
Coenzyme Q10 for ALS 317
COX-2 inhibitors for ALS 317
Dexpramipexole 317
Diallyl trisulfide 318
Erythropoietin for ALS 318
Gene therapy for ALS 318
Glatiramer acetate 319
Insulin-like growth factor 319
Ketogenic diet for neuroprotection in ALS 320
Lenalidomide 320
Lithium for neuroprotection in ALS 321
Methylcobalamin 321
Minocycline for ALS 321
Olesoxime as neuroprotective for ALS 321
ONO-2506 for ALS 322
Riluzole 322
RNAi-based therapy for ALS 322
Sodium phenylbutyrate 323
Stem cell therapy 323
Talampanel 323
Tamoxifen 323
Vaccination for ALS caused by SOD1 mutations 324
Vascular endothelial growth factor for ALS 324
Vitamin E for ALS 324
Clinical trials of neuroprotective therapies for ALS 325
Concluding remarks and future prospects 327
11. Neuroprotection in Miscellaneous Neurological Disorders 329
Introduction 329
Age-related dementia 329
Enhancing endogenous neurotrophic support of the aging brain 329
Pharmacological approaches for treatment of age-related dementia 330
Physical exercise to prevent decline of mental function with aging 331
Vascular dementia 331
Prediction of dementia in persons with vascular risk factors 331
Management of subcortical vascular dementia 332
Dementia with Lewy bodies 333
Neuroprotection in AIDS dementia 333
Multiple system atrophy 334
Epilepsy 334
Mechanisms of neuronal damage in epilepsy 334
Strategies for neuroprotection in epilepsy 335
Control of seizures by AEDs and neuroprotection 336
Prevention of seizures by ketogenic diet 337
Cell therapy for neuroprotection in epilepsy 338
Cell therapy of posttraumatic epilepsy 338
Cell therapy for temporal lobe epilepsy 338
Cell therapy for pharmacoresistant epilepsies 339
Gene therapy for neuroprotection in epilepsy 339
Spinal and bulbar muscular atrophy 340
Spinal muscular atrophy 340
Multiple sclerosis 341
Introduction 341
Epidemiology of multiple sclerosis 341
Pathophysiology 342
Current management of multiple sclerosis 342
Specific therapies for MS based on pathomechanism 343
Neuroprotection in multiple sclerosis 343
Clinical trials of neuroprotective therapies for MS 344
Neuroprotection by control of progressive forms of multiple sclerosis 347
Neuroprotection by controlling autoimmune inflammation in the brain 347
Remyelination for neuroprotection in multiple sclerosis 348
Agents for neuroprotection in multiple sclerosis 348
Angiotensin-II inhibitors 348
Antiglutamate agents 348
Antioxidants for neuroprotection in MS 348
Antisense and RNAi approaches to MS 349
Cell therapy for multiple sclerosis 349
Cladribine 351
Dalfampridine in MS 352
Dimethyl fumarate 352
DNA vaccine for MS 352
Erythropoietin as a neuroprotective in MS 353
Fingolimod (FTY720) 353
Fusokine composed of GM-CSF and IL-15 for immune suppression 354
Gene therapy for MS 354
Ibudilast for MS 354
IVIG for MS 355
Kinase inhibitors 355
Laquinimod 355
Monoclonal antibodies for MS 355
Natalizumab 356
Natural human antibodies for repair of myelin 356
Neurotrophic factors for multiple sclerosis 357
Oral immunomodulatory agents for MS 358
Recombinant T-cell ligands 358
Statins for MS 358
Teriflunomide 359
Concluding remarks on neuroprotection in MS 359
Neuroprotection in transverse myelitis 359
Neuroprotection in decompression sickness 360
Neuroprotection in CSF circulatory disorders 361
Neuroprotection in hydrocephalus 361
Neuroprotection in normal pressure hydrocephalus 361
Neuroprotection in infections of the CNS 362
Neuroprotection in bacterial meningitis 362
Mechanism of neural injury in bacterial meningitis 362
Strategies for neuroprotection 363
Neuroprotective approach to rabies 363
Neuroprotection in cerebral malaria 363
Neuroprotection in hypertensive encephalopathy 364
Neuroprotection in toxic encephalopathies 364
Hepatic encephalopathy 364
Management of hepatic encephalopathy 365
Encephalopathy due to organophosphorus poisoning 365
Neuroprotection against chemotherapy-induced brain damage 366
Neuroprotection against alcohol 366
Alcoholic neurologic disorders 366
Fetal alcohol syndrome 367
Pathogenesis of alcohol-induced damage to the nervous system 367
Neuroprotection against neurotoxicity of alcohol 367
Neuroprotection in hypoxia-ischemia 368
Neuroprotection in neonatal hypoxic-ischemic brain injury 368
Minocycline for neonatal hypoxia-ischemia 369
Nicotinamide mononucleotide adenylyl transferase 1 369
Nitric oxide inhalation for neonatal hypoxia-ischemia 369
Plasminogen activator inhibitor-1 for neonatal hypoxia-ischemia 370
Recombinant erythropoietin for neonatal hypoxia-ischemia 370
Neuroprotection in carbon monoxide poisoning 370
Pathomechanism of CO poisoning as a basis for neuroprotection 371
Management of CO poisoning 371
Syndrome of delayed post-hypoxic leukoencephalopathy 372
Neuroprotection of the fetus 372
Neuroprotection in sleep apnea 373
Neuroprotection in hypoglycemic coma 373
Neuroprotection in mitochondrial dysfunction 374
Mitochondrial permeability transition 374
Mitochondrial approaches for neuroprotection 375
Methylene blue 376
Role of nanolasers in evaluation of mitochondrial neuroprotectants 376
Neuroprotection in mitochondrial encephalopathies 376
Neuroprotection in psychiatric disorders 377
Cognitive impairment in schizophrenia 377
Neuroprotection in schizophrenia 377
Electroconvulsive therapy and neuroprotection 378
Neuroprotection in hearing loss 378
Causes of hearing loss 378
Pathomechanism of hearing loss 379
Prevention and treatment of hearing loss 379
Hyperbaric oxygen for hearing loss 380
Stem cell therapy for hearing loss 380
Auditory hair cell replacement by gene therapy 381
Pharmaceutical approaches to hearing loss 381
Neuroprotection of peripheral nerves 382
Neuroprotective agents for peripheral nerves 382
Acetyl-L-carnitine for peripheral nerve injurie
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