ASCORBATE ATTENUATES THE SYSTEMIC KAINATE-INDUCED NEUROTOXICITY IN THE RAT HIPPOCAMPUS

The neuronal damage induced by systemic administration of kainic acid reproduces the cellular and regional pattern of damage produced by rep eated seizures. The ability of kainic acid to induce lipid peroxidatio n, and the ability of free radical inhibitors to prevent ischaemically -induced cell death, has led us to examine the possible role of free r adicals in kainate-induced injury. Ascorbic acid was able to reduce ka inate-induced damage of the rat hippocampus, measured by means of the gliotic marker ligand [H-3]PK11195. Ascorbate was significantly effect ive at doses of 30 mg kg(-1) and above, with total protection against kainate at 50 mg kg(-1). Histologically, ascorbate at 50 mg kg(-1) was able to prevent kainate-induced neuronal loss in the hippocampal CA1 and CA3a cell layers. The antioxidant was also effective when administ ered simultaneously with, or 1 h before the kainate. Protection was al so obtained by allopurinol, 175 mg kg(-1) and by oxypurinol, 40 mg kg( -1). Ascorbate did not modify synaptically evoked potentials or long-t erm potentiation in hippocampal slices, ruling out any blocking activi ty at glutamate receptors. It is concluded that the neuronal damage pr oduced by systemically administered kainate involves the formation of free radicals.