Mechanisms of injury in hypoxic-ischemic encephalopathy: implications to therapy.

Cardiac arrest survivors commonly suffer ischemic brain injury, and understanding the mechanisms of injury is essential to providing insight for effective therapies for brain protection. Injury can occur at the time of the cardiac arrest and is dependent not only on the duration but also the degree of impaired circulation. Injury can be ongoing even after the return of spontaneous circulation, giving the clinician an additional window of opportunity to treat and protect the injured brain. This section will review the molecular basis of injury with cardiac arrest and will elucidate the different mechanisms of injury between cardiac arrest, pure respiratory arrest, and arrest secondary to toxins (e.g., carbon monoxide). The rationale for multiple postarrest therapies, such as hypothermia and induced hypertension, will also be reviewed.

[1]  D. Chamberlain,et al.  International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out‐of‐hospital cardiac arrest: The Thrombolysis in Cardiac Arrest (TROICA) Study , 2005, European journal of clinical investigation.

[2]  Alan D. Lopez,et al.  Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. , 2002, The New England journal of medicine.

[3]  J. Adams,et al.  The effects of systemic hypotension upon the human brain. Clinical and neuropathological observations in 11 cases. , 1966, Brain : a journal of neurology.

[4]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[5]  L. Caplan Reperfusion of Ischemic Brain: Why and Why Not! , 1991 .

[6]  Karen Smith,et al.  Treatment of Comatose Survivors of Out-of-hospital Cardiac Arrest With Induced Hypothermia , 2003 .

[7]  R. Myers,et al.  Neuropathology of systemic circulatory arrest in adult monkeys , 1972, Neurology.

[8]  W. Schwindt,et al.  Endothelin type A-antagonist improves long-term neurological recovery after cardiac arrest in rats , 2000, Critical care medicine.

[9]  R. Myers,et al.  The topography of impaired micro vascular perfusion in the primate brain following total circulatory arrest , 1972, Neurology.

[10]  H. Knobler,et al.  The role of hyperglycemia in acute stroke. , 2001, Archives of neurology.

[11]  A. Buchan,et al.  Hypothermia rescues hippocampal CA1 neurons and attenuates down-regulation of the AMPA receptor GluR2 subunit after forebrain ischemia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C. Epstein,et al.  Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion , 1998, The Journal of Neuroscience.

[13]  R. Raker,et al.  Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest: Brain Resuscitation clinical Trial I Study Group. N Eng J Med 314:397–403, (February), 1986 , 1987 .

[14]  S. Wagner,et al.  Metabolism of Glucose, Glycogen, and High-energy Phosphates during Complete Cerebral Ischemia: A Comparison of Normoglycemic, Chronically Hyperglycemic Diabetic, and Acutely Hyperglycemic Nondiabetic Rats , 1994, Anesthesiology.

[15]  B. Zalc,et al.  MRI identification of early white matter injury in anoxic–ischemic encephalopathy , 2001, Neurology.

[16]  M H Weil,et al.  Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. , 2003, Circulation.

[17]  Nicolás Vila,et al.  A Genetic Approach to Ischemic Stroke Therapy , 2003, Cerebrovascular Diseases.

[18]  P. Safar,et al.  Hypertension With Hemodilution Prevents Multifocal Cerebral Hypoperfusion After Cardiac Arrest in Dogs , 1992, Stroke.

[19]  R. Ichord,et al.  Treatment with the competitive NMDA antagonist GPI 3000 does not improve outcome after cardiac arrest in dogs. , 1998, Stroke.

[20]  S. Schwab,et al.  Effects of intracerebroventricular application of brain-derived neurotrophic factor on cerebral recovery after cardiac arrest in rats , 2004, Critical care medicine.

[21]  R. Auer,et al.  Hypoxia, hyperoxia, ischemia, and brain necrosis , 2000, Neurology.

[22]  F. Plum,et al.  Delayed neurological deterioration after anoxia. , 1962, Archives of internal medicine.

[23]  R. Gwinn,et al.  The effects in vivo of hypoxia on brain injury , 1996, Brain Research.

[24]  J. Edelsberg,et al.  Hyperbaric-oxygen therapy. , 1996, The New England journal of medicine.

[25]  F. Plum,et al.  Delayed hippocampal damage in humans following cardiorespiratory arrest , 1987, Neurology.

[26]  M. Copass,et al.  Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest , 2002, Neurology.

[27]  S. Hachimi-Idrissi,et al.  The effect of mild hypothermia and induced hypertension on long term survival rate and neurological outcome after asphyxial cardiac arrest in rats. , 2001, Resuscitation.

[28]  W. Landau,et al.  Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest , 2003, Neurology.

[29]  N. Pace,et al.  Acceleration of carbon monoxide elimination in man by high pressure oxygen. , 1950, Science.

[30]  J. LaManna,et al.  Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation , 1999, Brain Research.

[31]  M. Ruano,et al.  The neurologic effects of thiopental therapy after cardiac arrest , 1988, Intensive Care Medicine.

[32]  Peter T Morley,et al.  Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. , 2003, Circulation.

[33]  K. Hossmann,et al.  Resuscitation of the monkey brain after 1 h complete ischemia. I. Physiological and morphological observations. , 1974, Brain research.

[34]  M. Ginsberg,et al.  Hypoxic-ischemic leukoencephalopathy in man. , 1976, Archives of neurology.

[35]  H. Bitterman,et al.  [Hyperbaric oxygen for acute carbon monoxide poisoning]. , 1985, Harefuah.

[36]  G. Horner,et al.  Survival following extreme hypoxemia. , 1970, JAMA.

[37]  D. T. Ross,et al.  The AMPA antagonist NBQX protects thalamic reticular neurons from degeneration following cardiac arrest in rats , 1995, Brain Research.

[38]  M. Kowada,et al.  Cerebral ischemia. II. The no-reflow phenomenon. , 1968, The American journal of pathology.

[39]  D. Ferriero,et al.  Developmental expression of heme oxygenase-1 (HSP32) in rat brain: an immunocytochemical study. , 1998, Brain research. Developmental brain research.

[40]  K. Hossmann,et al.  Recovery of integrative central nervous function after one hour global cerebro-circulatory arrest in normothermic cat , 1987, Journal of the Neurological Sciences.

[41]  P. Safar,et al.  Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. , 1996, Stroke.

[42]  B. Cooper,et al.  Lamotrigine protects hippocampal CA1 neurons from ischemic damage after cardiac arrest. , 1997, Stroke.

[43]  C. Bode,et al.  Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial , 2001, The Lancet.

[44]  Andrew M. Johanos A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. , 1991, The New England journal of medicine.

[45]  F. Shibasaki,et al.  Calcineurin and cyclophilin D are differential targets of neuroprotection by immunosuppressants CsA and FK506 in ischemic brain damage. , 2003, Acta neurochirurgica. Supplement.

[46]  M. Bennett,et al.  Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. , 2002, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  S. Kraydieh,et al.  Regulation of caspases and XIAP in the brain after asphyxial cardiac arrest in rats , 2001, Neuroreport.