Anticonvulsant lamotrigine administered on reperfusion pails to improve experimental stroke outcomes

Background and Purpose-Recent results suggest that selective inhibitors of presynaptic neuronal ion channels can diminish glutamate release during cer ebral ischemia and modulate excitotoxic cell death. The aim of the present study was to evaluate lamotrigine (LTG), an antiepileptic that inhibits pre synaptic sodium and voltage-sensitive calcium channels, as a potential stro ke resuscitation agent in the rat. Three dosages of LTG were examined for e ffect on infarction volume and sensorimotor behavioral recovery after middl e cerebral artery (MCA) occlusion. Methods-Halothane-anesthetized male Wistar rats were subjected to 2 hours o f MCA occlusion by the intraluminal occlusion technique. Physiological vari ables were controlled, and ipsilateral cortical perfusion was monitored by laser Doppler flowmetry throughout ischemia. At onset of reperfusion, rats received intravenous LTG 5, 10, or 20 mg/kg or PBS (n=9 to 11 per group) du ring 15 minutes. Behavioral assessment was completed at 3 and 7 days after stroke, and the brain was harvested for histology (triphenyltetrazolium chl oride staining). Results-Values are mean+/-SE. Cortical infarction volumes were unchanged in LTG-treated animals: 14+/-6% of contralateral cortex at 5 mg/kg LTC, 17+/- 7% at 10 mg/kg, and 30+/-6% at 20 mg/kg, versus saline-treated cohorts (12/-3%; P=0.19; n=9). Caudate-putamen infarction injury was also unchanged (3 7+/-11% of contralateral caudate-putamen at 5 mg/kg LTG, 44+/-8% at 10 mg/k g, and 65+/-9% at 20 mg/kg versus saline (38+/-11%; P=0.18). Total infarcti on was not different among groups (P=0.15). Consistent with histology, beha vioral outcomes were unimproved by treatment. Conclusions-Histological damage and behavioral recovery at 7 days after MCA occlusion was not altered by LTG treatment over the dosage range used in t he present study.