THE ENDOGENOUS COFACTORS, THIOCTIC ACID AND DIHYDROLIPOIC ACID, ARE NEUROPROTECTIVE AGAINST NMDA AND MALONIC-ACID LESIONS OF STRIATUM

Thioctic acid (alpha-lipoic acid) and dihydrolipoic acid are endogenou s, interconvertible cofactors of the mitochondrial pyruvate dehydrogen ase and alpha-ketoglutarate dehydrogenase complexes. These compounds h elp to maintain glutathione and alpha-tocopherol in their reduced stat es, and they possess intrinsic free radical scavenging properties. We examined whether systemic treatment with thioctic acid or dihydrolipoi c acid is protective against direct- and indirect-acting excitotoxins. Adult rats were treated for 10 days with intraperitoneal injections o f vehicle, thioctic acid or dihydrolipoic acid, and on day 7 of treatm ent animals received unilateral stereotaxic injections of NMDA or malo nic acid into the striatum. Histological assessment 3 days after the s tereotaxic injections revealed a marked reduction in lesion volume in animals treated with thioctic acid or dihydrolipoic acid. We conclude that thioctic acid and dihydrolipoic acid are neuroprotective against direct and indirect excitotoxic insults.