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 cerebral arterial (MCA) ligation-induced cortical infarction in rats. Recent studies 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 investigate if administration of D3 in vivo will protect against ischemic brain injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for four or eight days. Animals received a 90-min right MCA ligation 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 after the onset of reperfusion. A subset of animals receiving eight days of D3 or saline treatment were used for blood gas and cerebral GDNF protein level analysis. We found that pretreatment with D3 for four days did not attenuate the ischemic injury. However, animals receiving eight days of D3 injections showed a significant reduction in the amount of infarction in the cortex. Eight day D3 treatment did not alter blood gases or blood pressure; however, it did increase calcium levels. Pretreatment with D3 significantly increased GDNF levels in the cortex. In conclusion, our data indicate that D3 reduces ischemia-induced brain damage and supports the hypothesis that this effect may be through the up-regulation of GDNF mechanisms in cortex.
Wang
Y
Y
National Institute on Drug Abuse, NIH, Baltimore, MD, USA. ywang@intra.nida.nih.gov
Chiang
Y H
YH
Su
T P
TP
Hayashi
T
T
Morales
M
M
Hoffer
B J
BJ
Lin
S Z
SZ
D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002762:Cholecalciferol / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006454:Hemoglobins / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D001786:Blood Glucose; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006454:Hemoglobins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D002762:Cholecalciferol; D002118:Calcium