REGIONAL AND TEMPORAL PROFILES OF CALCIUM ACCUMULATION AND GLIAL FIBRILLARY ACIDIC PROTEIN-LEVELS IN RAT-BRAIN AFTER SYSTEMIC INJECTION OF KAINIC ACID

Cerebral calcium accumulation and increases in the astroglial intermed iate filament protein, glial fibrillary acidic protein (GFAP), have be en used as markers of neurotoxic and ischemic brain damage. The presen t study was aimed at quantitatively investigating the regional and tem poral relationship of those indices following a neurotoxic insult. For this purpose, regional changes in Ca-45 uptake and GFAP levels, using ELISA, were evaluated in rat brains at both early (several hours) and late time points (up to 6 months) after a single systemic injection o f kainic acid (12 mg/kg). After 4 h, limbic brain areas were already h eavily labelled by Ca-45. In most investigated brain areas Ca-45 accum ulation peaked at day 4 (maximum 5 fold increase in amygdala) and retu rned to normal levels within 1 week (cerebellum, pons/medulla, occipit al cortex), 2 weeks (striatum, frontal cortex), 2 or 4 months (limbic brain areas), or remained significantly elevated until 6 months (thala mus). In contrast, in all investigated brain areas, except cerebellum and pons/medulla, GFAP was increased from day 2, reaching maximum leve ls at day 28 in most limbic structures and remained significantly elev ated at the same high level (15 fold increase) in amygdala, or somewha t lower levels in other affected regions (2-7 fold), but not in the th alamus. In all brain areas with Ca-45 accumulation, GFAP was increased and the peak responses were highly correlated. Thus, both indices are useful quantitative biochemical markers of acute or subchronic neurot oxicity.