ISCHEMIA AND LESION-INDUCED IMBALANCES IN CORTICAL FUNCTION

Cortical structures are often critically affected by ischemic and trau matic lesions which may cause transient or permanent functional distur bances, These disorders consist of changes in the membrane properties of single cells and alterations in synaptic network interactions withi n and between cortical areas including large-scale reorganizations in the representation of the peripheral input. Prominent functional modif ications consisting of massive membrane depolarizations, suppression o f intracortical inhibitory synaptic mechanisms and enhancement of exci tatory synaptic transmission can be observed within a few minutes foll owing the onset of cortical hypoxia or ischemia and probably represent the trigger signals for the induction of neuronal hyperexcitability, irreversible cellular dysfunction and cell death, Pharmacological mani pulation of these early events may therefore be the most effective app roach to control ischemia and lesion induced disturbances and to atten uate long-term neurological deficits. The complexity of secondary stru ctural and functional alterations in cortical and subcortical structur es demands an early and powerful intervention before neuronal damage e xpands to intact regions, The unsatisfactory clinical experience with calcium and N-methyl-D-aspartate antagonists suggests that this result might be achieved with compounds that show a broad spectrum of action s at different ligand-activated receptors, voltage-dependent channels and that also act at the vascular system. Whether the same therapy str ategies developed for the treatment of ischemic injury in the adult br ain may be applied for the immature cortex is questionable, since youn g cortical networks with a high degree of synaptic plasticity reveal a different response pattern to hypoxic and ischemic insults. Age-depen dent molecularbiological, morphological and physiological parameters c ontribute to an enhanced susceptibility of the immature brain to these noxae during early ontogenesis and have to be investigated in more de tail for the development of adequate clinical therapy.