Rvw. Dimlich et Pj. Marangos, DICHLOROACETATE ATTENUATES NEURONAL DAMAGE IN A GERBIL MODEL OF BRAINISCHEMIA, Journal of molecular neuroscience, 5(2), 1994, pp. 69-81
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.