Studies on the Pathogenesis of Ischemic Brain Damage and Its Amelioration by Barbiturate Therapy

Abstract

Past studies have resulted in two major concepts in our understanding of the pathogenesis of ischemic brain damage (Fig. 1). First, the demonstration that barbiturates (1, 15, 16, 23) and flow-promoting (19) therapies applied after global brain ischemia markedly attenuate the ultimate degree of neurological dysfunction sustained suggests that much of the damage occurs after restoration of circulation. Secondly, reports that during anoxia, brain electric failure occurs before any evidence of metabolic failure (5, 12, 13) and that postanoxia, brain metabolites are normal before spontaneous electric activity returns (10, 11) suggest that neurological dysfunction after cerebral ischemic anoxia results from a combination of both neuronal necrosis and failure in synaptic transmission perhaps secondary to neurotransmitter dysfunction (Fig. 1). Loss of neurotransmitter regulatory mechanisms may also contribute to the pathophysiologic and biochemical changes leading to further neuronal necrosis. Failure of synaptic transmission in ischemic anoxic brain damage is supported by the findings that synaptic transmission is most susceptible to anoxia (3, 8).