PREEXPOSURE TO SUBTOXIC LEVELS PREVENTS KAINIC ACID LESIONS IN ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES - EFFECTS OF KAINIC ACID ON PARVALBUMIN-IMMUNOREACTIVE NEURONS AND EXPRESSION OF HEAT-SHOCK PROTEIN-72 FOLLOWING THE INDUCTION OF TOLERANCE

The effects of kainic acid on the survival of principal neurons and pa rvalbumin-immunoreactive (PARV-IR) neurons, and on the expression of h eat shock protein 72 immunoreactivity (HSP72-IR) were investigated in organotypic hippocampal slice cultures. Untreated cultures displayed a n organotypic organization and the development and morphology of PARV- IR neurons in the hippocampus paralleled that reported to occur in viv o, with the exception of the hilar region of the dentate gyrus which e xhibited a marked lack of PARV-IR neurons. No constitutive expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons an d the reduction in numbers of PARV-IR neurons in both CA3 and CA1 afte r chronic exposure to 5 mu M kainic add were similar to those reported to occur in vivo. Exposure to 1 mu M doses of kainic acid resulted in a widespread appearance of HSP72-IR and the induction of tolerance to a previously toxic dose of kainic acid. These results suggest the pre sence of endogenous neuroprotective mechanisms, activated by a stress response which induces HSP72, and is reminiscent of the induced tolera nce reported to occur after a mild ischaemic insult.