Can we reverse ischemic penumbra? Some mechanisms in the pathophysiology of energy-compromised brain tissue

The region surrounding a focal cerebral infarct shows selective rather than generalized neuronal damage. The "ischemic penumbra" has been defined electrophysiologically as that region which shows a loss of electrical activity while retaining some metabolic viability (Astrup et al., Stroke, 1981:6:723-5). How factors that contribute to ischemic damage may cause such selective damage to subpopulations of neurones will be discussed. Particular attention will be directed to the cortical pyramidal cells, thought to be a major component of cerebral electrical activity. The N-methyl-D-aspartate (NMDA) class of glutamic acid receptors appears to have a role in certain aspects of ischemic damage, mediated through excitotoxins and calcium ions. The regulation of this receptor complex appears to be unaffected by ischemia, and thus it may provide a target for possible therapeutic interventions. Selective neuronal loss tends to be associated with neurotransmitter imbalance; therefore, treatments designed to correct this imbalance by affecting the activity of those cells less sensitive to ischemia may provide an alternative approach to establish normal cerebral function.