Innate Tolerance in the CNS [recurso electrónico] Translational Neuroprotection by Pre- and Post-Conditioning

Cerebral preconditioning is a phenomenon wherein a mild insult or stress induces cellular and tissue adaptation or tolerance to a later, severe injury, therefore reflecting the efficacy of endogenous mechanisms of cerebrovascular protection. Initially identified for rapid cardiac protection, preconditioning has expanded to all aspects of CNS protection from ischemia, trauma and potentially neurodegeneration. Many different stimuli or stressors have been identified as preconditioning agents, suggesting a downstream convergence of mechanisms and underscoring the potential for translational application of preconditioning in the clinic. Moreover, the fundamental mechanisms responsible for preconditioning-induced tolerance will help in the design novel pharmacological approaches for neuroprotection. While stroke and many other brain injuries are not predictable, in some populations (e.g., metabolic syndrome, patients undergoing carotid endarterectomy, aneurysm clipping, or with recent TIAs) the risk for stroke is identifiable and significant, and preconditioning may represent a useful strategy for neuroprotection. For unpredictable injuries, post-conditioning the brain – or inducing endogenous protective mechanisms after the initial injury – can also abrogate the extent of injury. Finally, remote pre- and post-conditioning methods have been developed in animals, and are now being tested in clinical trials, wherein a brief, noninjurious stress to a noncerebral tissue (i.e., skeletal muscle) can provide protection to the CNS and thereby allows clinicians the opportunity to circumvent concerns regarding the direct preconditioning of neurological tissues. Front Matter....Pages i-ix Front Matter....Pages 1-1 Tolerance, Historical Review....Pages 3-18 Anoxia Resistance in Lower and Higher Vertebrates....Pages 19-35 Hibernation: A Natural Model of Tolerance to Cerebral Ischemia/Reperfusion....Pages 37-50 Preconditioning in the Heart....Pages 51-101 Front Matter....Pages 103-103 Neuroprotection and Physical Preconditioning: Exercise, Hypothermia, and Hyperthermia....Pages 105-131 A New Future in Brain Preconditioning Based on Nutraceuticals: A Focus on α-Linolenic Omega-3 Fatty Acid for Stroke Protection....Pages 133-163 Medical Gases for Conditioning: Volatile Anesthetics, Hyperbaric Oxygen, and Hydrogen Sulfide....Pages 165-181 Hypoxic Preconditioning in the CNS....Pages 183-212 Pharmacologic Preconditioning....Pages 213-224 Surgical Methods to Induce Brain Preconditioning....Pages 225-240 Front Matter....Pages 241-241 Tolerance Against Global Cerebral Ischemia: Experimental Strategies, Mechanisms, and Clinical Applications....Pages 243-257 Preconditioning and Neuroprotection in the Immature Brain....Pages 259-268 Conditioning Studies in Focal Cerebral Ischemia: Model Selection, Physiological Monitoring, and Other Methodological Issues....Pages 269-289 Preconditioning for SAH....Pages 291-308 Preconditioning and Intracerebral Hemorrhage....Pages 309-316 The Protective Effects of Ischemic Postconditioning in Experimental Stroke....Pages 317-335 Front Matter....Pages 337-337 Synaptic Signaling in Ischemic Tolerance....Pages 339-361 The Genomics of Preconditioning and Ischemic Tolerance....Pages 363-386 How Do Subcellular Organelles Participate in Preconditioning-Conferred Neuroprotection?....Pages 387-427 Ischemic Preconditioning-Mediated Signaling Pathways Leading to Tolerance Against Cerebral Ischemia....Pages 429-455 Front Matter....Pages 337-337 Preconditioning the Neurovascular Unit: Tolerance in the Brain’s Nonneuronal Cells....Pages 457-481 Front Matter....Pages 483-483 Preconditioning for Surgical Brain Injury....Pages 485-498 Intrinsic Neuroprotection in Traumatic Brain Injury....Pages 499-519 Preconditioning for Epilepsy....Pages 521-539 Ischemic Pre- and Post-conditioning in the Retina....Pages 541-550 Front Matter....Pages 551-551 Clinical Cerebral Preconditioning and Postconditioning....Pages 553-566 Preconditioning Strategy: Coronary Bypass, Subarachnoid Hemorrhage, Temporary Proximal Vessel Occlusion in Carotid Revascularization, and Intracranial Aneurysm Surgery....Pages 567-577 HBO Preconditioning for TBI and Stroke Patients....Pages 579-589 Electroacupuncture Preconditioning for Stroke Patients....Pages 591-599 Clinical Trials of Ischemic Conditioning....Pages 601-613 Back Matter....Pages 615-699 Cerebral ischemia from cardiac arrest, stroke, and subarachnoid and intracerebral hemorrhage, together with trauma, epilepsy, and other CNS pathologies, continue to impose immense burdens of morbidity and mortality the world over. Despite many decades of research aimed at understanding the genetic and molecular basis of these pathologies, therapeutics developed on the basis of blocking 'known injury mechanisms can actually claim few clinical successes. The field of CNS "preconditioning" was born from the preclinical finding more than 20 years ago that intentional activation of innate, cytoprotective factors could provide robust protection, or "tolerance" against cerebral ischemic injury. Herein, up-to-date summaries on all aspects of preconditioning for CNS disease, including the emerging topics of postconditioning and remote pre- and post-conditioning, are provided by the leading scientists in the field. The translational potential of both preclinical and clinical advances is underscored throughout, with the hope of accelerating the bench-to-bedside success of endogenous cytoprotection as a therapeutic strategy. Jeffrey M. Gidday PhD, Associate Professor of Neurosurgery at Washington University School of Medicine, has been working in the field of CNS preconditioning for 18 years, and has numerous publications on preconditioning-induced protection in the setting of several different cerebral and retinal pathologies. Miguel A. Perez-Pinzon PhD is Professor of Neurology/Neuroscience, Vice-Chair for Basic Science of Neurology at the University of Miami Miller School of Medicine. He began studies of ischemic preconditioning in 1995 and for many years prior to that worked in the field of anoxia tolerance, publishing close to 50 peer-reviewed articles and many book chapters on these topics. John H. Zhang MD PhD is Professor of Neurosurgery, Anesthesiology, and Physiology, and Vice-Chair of the Basic Science Department at the Loma Linda University Schoo l of Medicine. His research interests include stroke and medical gases, and he has published papers related to pre-, post- and remote-conditioning in subarachnoid hemorrhage, focal cerebral ischemia, and neonatal brain injury