Dichloroacetate attenuates neuronal damage in a gerbil model of brain ischemia.

ABSTRACT

Dichloroacetate facilitated a reduction in brain lactate following ischemia in the gerbil. This treatment also improved high-energy metabolite and pyruvate dehydrogenase enzyme recovery. The purpose of this study was to determine the effect of dichloroacetate on ischemia-induced neuronal damage in the hippocampus of the gerbil. In adult male gerbils, carotid arteries were clamped bilaterally for 5 min. After ischemia, each gerbil was graded neurologically and received an ip injection of dichloroacetate (75 or 225 mg/kg) or an equal volume (5 mL/kg) of sodium acetate (66 mg/kg). On the following morning, gerbils received a second injection, and 3 d later were anesthetized and perfused intracardially. Brains were processed, and stained sections were analyzed for neuronal damage. Gerbils treated with 225 mg/kg dichloroacetate exhibited significantly less damage than the untreated group (p = 0.05, Dunn's test). Gerbils with a normal neurologic score evidenced no neuronal damage. Abnormal neurologic scores immediately after ischemia did not correlate with degree of neuronal damage observed 4 d later. These results indicate that neuronal damage is less in gerbils treated after ischemia with an appropriate dose of dichloroacetate. The lack of any histological evidence for an adverse effect of dichloroacetate in the controls supports the safety of this drug in this protocol. Normal neurologic scores immediately after ischemia can be used to identify gerbils mimicking ischemia in this model.