FOS PROTEIN INDUCTION, NEUROPATHOLOGY, AN D PHARMACOLOGICAL PROTECTION AFTER EXCITOTOXIC BRAIN INSULT

The excitotoxins kainic acid and N-methyl D-aspartate (NMDA) were unil aterally injected in the rat striatum. Kainic acid injections resulted in a widespread pattern of Fos protein induction, mainly involving co rtical olfactory structures and hippocampus. Immunoreactive cells were observed in large number 2-24 h after injection and had almost comple tely disappeared by 48 h. NMDA injections elicited a shorter (2-8 h) e xpression of Fos protein, involving a lower number of cells in cortica l olfactory structures, a much larger number of cells in the other cor tical regions, and not involving the hippocampus at all. Characteristi cally none of the two excitotoxins stimulated Fos expression from stri atal neurons, even in the close vicinity of the needle tract. In addit ion to striatal lesions almost equivalent in size, the two excitotoxin s caused distant lesions of different extension: kainic acid resulted in extensive neuronal degeneration in the olfactory-entorhinal cortice s and among pyramidal neurons of the hippocampus; NMDA caused a less w idespread neurodegeneration, restricted to the olfactory cortex. Admin istration of the competitive NMDA antagonist CGP 39551 largely prevent ed the distant, but not the local, neuropathological changes caused by intrastriatal kainic acid or NMDA. The expression of Fos protein, how ever, was partially prevented only in NMDA cases. The present results show a good relationship between the spreading of circuit overexcitati on caused by the two excitotoxins and the regional and temporal patter ns of Fos expression. The relationship between Fos expression and neur opathological condition remains, however, elusive.