Amplification of inhibitory mechanisms in cerebral ischemia: an alternative approach to neuronal protection

• Shuaib, A. ^[2] ; Kanthan, R. ^[1]
  1. [1] University of Saskatchewan

     University of Saskatchewan

     Canadá

     
  2. [2] Department Medicine, George Washington University Medical Center, Washington DC, USA; Department of Pathology and Medicine, College of Medicine University of Saskatchewan, Saskatoon, Canada
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 12, Nº. 1, 1997, págs. 185-194
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • The central nervous system consumes 20% of the cardiac output for normal function. The neurons are very sensitive to the effects of ischemia. Cessation of cerebral blood flow results in severe damage to neurons and other brain structures. This is secondary to a combination of energy loss , excessive excitation promoting intracelJular calcium (Ca2+) buildup, relative lack of inhibitory responses, generation of oxygen free radicals (especially during the reperfusion period) and several other destructive cascades. Medications that antagonize the effects of glutamate at post-synaptic receptors are either ineffective or have serious sideeffects. Ca2+ entry blockers have shown disappointing results in clinical trials in patients with acute cerebral infarction. Data with protective effects of oxygen free radical scavengers in the post-ischemic period have shown conflicting results.

    There is recent interest with the use of agents that increase cerebral inhibitory responses after an ischemic insult. Such agents are effective when used before, during or up to 4 hours after the ischemic insult. Many such medications have few side-effects and are in clinical use for other indications. This review will summarize inhibitory mechanisms that may be important in cerebral ischemia, and provide experimental evidence for their potential efficacy.