Stroke Traumatic Brain and Spinal Cord Injuries

E D Hall, Spinal Cord and Brain Injury Research Center, University of Kentucky Medical Center, Lexington, KY, USA

© 2007 Elsevier Ltd. All Rights Reserved.

6.10.1 Disease State/Diagnosis 253

6.10.2 Disease Basis 254 Potential for Neuroprotective Drug Discovery 254 Overview of Secondary Central Nervous System Injury 254

6.10.3 Experimental Disease Models 256 Focal Ischemic Stroke Models 256 Hemorrhagic Stroke Models 258 Traumatic Brain Injury Models 258 Subdural Hematoma Model 258 Spinal Cord Injury Models 258

6.10.4 Clinical Trial Issues 259 Glutamate Antagonists 259 Calcium Channel Blockers 259 Free Radical Scavengers/Antioxidants 259 Dexanabinol (HU-211) 261 Lessons Learnt from Past Clinical Trials of Neuroprotective Agents 261 Biomarkers for Neuroprotective Drug Evaluation 262

6.10.5 Current Treatment 263 Stroke 263 Aneurysmal Subarachnoid Hemorrhage 263 Traumatic Brain Injury 263 Spinal Cord Injury 263

6.10.6 Unmet Medical Need 265

6.10.7 New Research Areas 266 New Concept Concerning Glutamate-Mediated Excitotoxicity 266 Newer Antioxidant Approaches 266 Prevention of Mitochondrial Dysfunction 269 Inhibition of Calpain-Mediated Proteolytic Damage 271 Anti-Inflammatory Strategies 272 Inhibition of Apoptotic Neurodegeneration 273 Thyrotropin-Releasing Hormone Analogs 275 Neurorestorative Drug Discovery 275 References 275

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