INDOLE PYRUVIC-ACID TREATMENT REDUCES DAMAGE IN STRIATUM BUT NOT IN HIPPOCAMPUS AFTER TRANSIENT FOREBRAIN ISCHEMIA IN THE RAT

The effects of treatment with indole-pyruvic acid, an endogenous metab olite of tryptophan converted into kynurenic acid in the brain, were s tudied in rats after transient forebrain ischemia induced by the 4-ves sel occlusion procedure. The histological analysis showed a significan t protective effect of indole pyruvic acid treatment on striatal ische mic lesions assessed by the extent of regional atrophy and the area of neuronal disappearance 14 days after ischemia. Striatal neurons were labelled by dopamine and adenosine 3':5'monophosphate regulated phosph oprotein-32 immunoreactivity. Conversely, increased neuronal loss, reg ional atrophy and glial fibrillary acidic protein immunoreactivity, an index of post-injury astroglial activation, were observed in the hipp ocampal formation, especially the CA3 field, of indole-pyruvic acid-tr eated rats when compared with vehicle-treated ischemic rats. The treat ment with indole-pyruvic acid did not produce any improving effects in a test assessing short-term impairments after transient ischemia (mot or test score at 24 h and 48 h post-ischemia). Furthermore, no signifi cant effects of indole-pyruvic acid treatment were found on performanc e in water T-maze studied at 7 and 14 days post-ischemia. The opposite effects of indole pyruvic acid on ischemic lesion in different brain regions may be related to its multiple neurochemical actions in the br ain. The protective effect of indole pyruvic acid on ischemic damage i n striatum may be due to its conversion into kynurenic acid, a broad s pectrum glutamate receptor antagonist. At hippocampal level, where glu tamate receptor antagonists have been proved ineffective in the presen t lesion model, indole-pyruvic acid-induced changes in monoamine avail ability may lead to a worsening of neuronal damage.