REGIONAL EXPRESSION OF INDUCIBLE HEAT-SHOCK PROTEIN-70 MESSENGER-RNA IN THE RAT-BRAIN FOLLOWING ADMINISTRATION OF CONVULSANT DRUGS

Expression of inducible heat shock protein-70 mRNA (hsp-70 mRNA) was s tudied in the rat brain following systemic administration of different convulsant agents: an L-type voltage-dependent calcium channel agonis t, (+/-)-BAY K 8644 (BAY-K); the excitotoxic glutamate agonists kainic acid and N-methyl-D-aspartic acid (NMDA); and the GABA, receptor comp lex antagonists pentylenetetrazole (PTZ) and lindane (gamma-hexacloroc yclohexane). BAY-K induced minimal hsp-70 mRNA expression in the hippo campus of convulsant rats, localized in the dentate gyrus and the pyra midal cell layer of Ammon's horn. Kainic acid treatment in rats, showi ng severe limbic convulsions, caused intense expression of hsp-70 mRNA and protein (HSP-70). Expression was localized in select cerebral reg ions, notably the pyramidal cell layer of the hippocampal CA3 field of Ammon's horn and the piriform cortex, and also the subicular complex and the amygdala, and, to a lesser extent, the entorhinal cortex, the pyramidal cell layer of CA1, several thalamic nuclei, and the parietal cortex. In contrast, systemic administration of NMDA, PTZ or lindane led to no detectable induction of hsp-70 mRNA in the rat brain, despit e producing convulsions. Histological examination revealed cell injury only following kainic acid treatment. Damage was most apparent in the piriform and entorhinal cortices, pyramidal cell layer of the CA1 fie ld, and cortical amygdaloid nuclei. BAY-K, NMDA, PTZ and lindane did n ot lead to any observable histopathological changes. These results sho w that convulsions of different aetiology do not inevitably induce hsp -70 mRNA expression or cell damage. Intense expression of hsp-70 mRNA was generally associated with regions that later showed variable degre es of nerve cell damage, although hsp-70 mRNA expression was not alway s predictive of subsequent cell death or survival.