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 repeated seizures. The ability of kainic acid to induce lipid peroxidation, and the ability of free radical inhibitors to prevent ischaemically-induced cell death, has led us to examine the possible role of free radicals in kainate-induced injury. Ascorbic acid was able to reduce kainate-induced damage of the rat hippocampus, measured by means of the gliotic marker ligand [3H]PK11195. Ascorbate was significantly effective 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 administered simultaneously with, or 1 h before the kainate. Protection was also obtained by allopurinol, 175 mg kg-1 and by oxypurinol, 40 mg kg-1. Ascorbate did not modify synaptically evoked potentials or long-term potentiation in hippocampal slices, ruling out any blocking activity at glutamate receptors. It is concluded that the neuronal damage produced by systemically administered kainate involves the formation of free radicals.
MacGregor
D G
DG
University of Glasgow, UK.
Higgins
M J
MJ
Jones
P A
PA
Maxwell
W L
WL
Watson
M W
MW
Graham
D I
DI
Stone
T W
TW
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007546:Isoquinolines / Q000378:metabolism; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009928:Organ Specificity; D010117:Oxypurinol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D007546:Isoquinolines; D018696:Neuroprotective Agents; D018048:Receptors, Purinergic P2; D010117:Oxypurinol; D001205:Ascorbic Acid; D007608:Kainic Acid; C037850:PK 11195