PHARMACOLOGICAL MANIPULATION OF THE NMDA RECEPTOR DIFFERENTIALLY PROTECTS FROM SYSTEMIC KAINIC ACID NEUROPATHOLOGY - EVALUATION THROUGH ORNITHINE DECARBOXYLASE INDUCTION, MORPHOLOGY AND GFAP IMMUNOHISTOCHEMISTRY

The excitotoxic brain damage caused by systemic administration of kain ic acid requires the activation of N-methyl-D-aspartate (NMDA) recepto rs in order to fully express its neurotoxic potency. We have tested th e relative efficacy of different manipulations of the NMDA receptor on morphological, immunohistochemical and neurochemical parameters in th is experimental model. A competitive (CGP 39551) and a non-competitive (MK 801) antagonist of the NMDA receptor, granted full protection aga inst neuronal degeneration and consequent glial proliferation in the h ippocampus and olfactory cortex, two regions severely affected by syst emic administration of kainic acid. In addition, CGP 39551 completely counteracted the dramatic induction of the enzyme ornithine decarboxyl ase which occurs shortly after kainic acid administration. Systemic ad ministration of high amounts of MgSO4 concomitantly and after kainic a cid injection, appeared to partially prevent neuronal degeneration but had no clear effects on glial reaction and ornithine decarboxylase in duction. Finally administration of an antagonist of the polyamine site present in the NMDA receptor (SL 82.0715), did not appear to have any protective effect at the dose used here. The present results help to better understand the ways by which it could be possible to counteract excitotoxic brain injuries.