DICHLOROACETATE ATTENUATES NEURONAL DAMAGE IN A GERBIL MODEL OF BRAINISCHEMIA

Dichloroacetate facilitated a reduction in brain lactate following isc hemia in the gerbil. This treatment also improved high-energy metaboli te and pyruvate dehydrogenase enzyme recovery. The purpose of this stu dy was to determine the effect of dichloroacetate on ischemia-induced neuronal damage in the hippocampus of the gerbil. In adult male gerbil s, carotid arteries were clamped bilaterally for 5 min. After ischemia , each gerbil was graded neurologically and received an ip injection o f dichloroacetate (75 or 225 mg/kg) or an equal volume (5 mL/kg) of so dium acetate (66 mg/kg). On the following morning, gerbils received a second injection, and 3 d later were anesthetized and perfused intraca rdially. Brains were processed, and stained sections were analyzed for neuronal damage. Gerbils treated with 225 mg/kg dichloroacetate exhib ited significantly less damage than the untreated group (p = 0.05, Dun n's test). Gerbils with a normal neurologic score evidenced no neurona l damage. Abnormal neurologic scores immediately after ischemia did no t correlate with degree of neuronal damage observed 4 d later. These r esults 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 neu rologic scores immediately after ischemia can be used to identify gerb ils mimicking ischemia in this model.