Vitamin D-3 attenuates cortical infarction induced by middle cerebral arterial ligation in rats

We have previously reported that intracerebral administration of glial cell line derived neurotrophic factor (GDNF) reduces the extent of middle cereb ral arterial (MCA) ligation-induced cortical infarction in rats. Recent stu dies have shown that application of 1,25 dihydroxyvitamin D-3 (D3) enhances GDNF mRNA expression in vitro. The purpose of the present study was to inv estigate if administration of D3 in vivo will protect against ischemic brai n injury. Adult male Sprague-Dawley rats were injected daily with D3 or wit h saline for four or eight days. Animals received a 90-min right MCA ligati on on the 4(th) or 8(th) day after anesthesia with chloral hydrate. Animals were sacrificed for tri-phenyl-tetrazolium chloride (TTC) staining 24 h af ter the onset of reperfusion. A subset of animals receiving eight days of D 3 or saline treatment were used for blood gas and cerebral GDNF protein lev el analysis. We found that pretreatment with D3 for four days did not atten uate the ischemic injury. However, animals receiving eight days of D3 injec tions showed a significant reduction in the amount of infarction in the cor tex. Eight day D3 treatment did not alter blood gases or blood pressure; ho wever, it did increase calcium levels. Pretreatment with D3 significantly i ncreased GDNF levels in the cortex. In conclusion, our data indicate that D 3 reduces ischemia- induced brain damage and supports the hypothesis that t his effect may be through the up-regulation of GDNF mechanisms in cortex. P ublished by Elsevier Science Ltd.