Abstract
Activation of presynaptic voltage-gated calcium channels and glutamate release serves a central role in neuronal necrosis after cerebral ischemia. Pregabalin binds to the α2-δ subunit of voltage-gated calcium channels and results in reduced glutamate release. The aim of the current study was to evaluate the effect of pregabalin on cerebral outcome following cerebral ischemia using an established rat model. Male Sprague-Dawley rats were randomized to receive oral administration of 5 mg/kg pregabalin for 1 day (PD1 group) or 5 days (PD5 group), or an equal amount of normal saline for 1 day (SD1 group) or 5 days (SD5 group) after 1 day of middle cerebral artery occlusion (MCAO) and reperfusion. Behavioral tests were assessed at postoperative days 1 and 7. Cerebral infarct volume was measured using a brain MRI scan on days 1 and 7 following surgery. Using immunohistochemistry to detect brain-derived neurotrophic factor (BDNF), histologic examinations of perilesional cortex and ipsilateral hippocampus were performed at postoperative day 7. BDNF-positive immunostaining was more abundant in the perilesional cortex of mice of the PD1 group compared with mice of the SD1 group (P=0.001). In the ipsilateral hippocampus, greater BDNF-positive staining was present in the PD5 group compared with the SD5 group (P=0.04). No statistically significant differences were indicated for behavioral tests or cerebral infarct volume between the PD1 and SD1 groups or the PD5 and SD5 groups. In conclusion, treatment with pregabalin beneficially impacts BDNF expression and histologic cerebral outcome in rats after cerebral ischemia.