Time- and dose-dependent 45Ca2+ accumulation in rat striatum and substantia nigra after an intrastriatal injection of quinolinic acid

To evaluate the use of cerebral 45Ca accumulation as an index for neurotoxic brain damage, the dose and time dependency of regional 45Ca accumulation in the rat brain following an unilateral injection of quinolinic acid (QUIN) into the striatum was investigated. Accumulation of radioactivity was assessed 6 h or 1, 2, 7, 21, 42, and 84 days after QUIN and 6 h or 1 day after ip 45CaCl2 injection using liquid scintillation counting of dissected brain tissues and semiquantitative autoradiography of brain sections. Dissected striata were also used for assay of glutamic acid decarboxylase (GAD) activity and after autoradiography brain sections were stained with thionine or for cholinesterase. One week after QUIN (0-50 micrograms) a dose-dependent increase in 45Ca accumulation in the injected striatum and the ipsilateral substantia nigra, but not in frontal cortex or cerebellum, was observed. In addition, 45Ca accumulation and GAD reduction in the striatum was highly significantly correlated. In the striatum 45Ca accumulated rapidly within 48 h and after this time point--by this time GAD had reached a minimum--the 45Ca content continued to increase in the lesioned striatum until Day 42. Six hours after QUIN 45Ca accumulated in the immediate vicinity of the injection site, whereas the increase 6 weeks later is primarily due to accumulation of 45Ca in striatal tissue more remote from the injection site. In the ipsilateral substantia nigra 45Ca accumulation reached a maximum 7 days after QUIN, probably reflecting delayed transneuronal death rather than degeneration of striatonigral nerve terminals.