cholecalciferol and Infarction--Middle-Cerebral-Artery

This study aims at investigating the neuroprotective role of Vitamin D3 (VitD3) in rats with cerebral infarction and its molecular mechanisms.. Male Sprague- Dawley (SD) rats were selected and randomly divided into sham operation group, middle cerebral artery occlusion (MCAO) model group, and VitD3 treatment group. The therapeutic effect of VitD3 was evaluated via neurobehavioral scoring and triphenyltetrazolium chloride (TTC) staining. For the evaluation of VitD3 influence on cerebral blood perfusion, Micro-PET imaging technique was applied. The mRNA levels of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) gene were detected via Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Immunofluorescence staining assay was employed to determine the changes in micro-vessel density. Bromodeoxyuridine (Brdu) assay was used to count the number of new vascular endothelial cells. Protein expressions of key genes in the Shh signaling pathway were detected by Western blotting.. Our results showed that VitD3 improved the score of neurological function and decreased the size of cerebral infarction in MCAO rats. VitD3 improved cerebral perfusion in the ischemic area after MCAO. VitD3 up-regulated levels of vascular growth-related factors. VitD3 elevated micro-vessel density after cerebral infarction and promoted the proliferation of vascular endothelial cells in the ischemic cortex. The sonic hedgehog (Shh) signaling pathway in the ischemic cortex of MCAO rats was activated after VitD3 treatment.. We showed that VitD3 improves cerebral perfusion and reduces neurological impairment in MCAO rats via activating the Shh signaling pathway.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Cerebral Infarction; Cholecalciferol; Endothelial Cells; Hedgehog Proteins; Infarction, Middle Cerebral Artery; Male; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Signal Transduction; Up-Regulation; Vascular Endothelial Growth Factor A

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.

Topics: Animals; Blood Gas Analysis; Blood Glucose; Blood Pressure; Calcium; Cerebral Cortex; Cholecalciferol; Enzyme-Linked Immunosorbent Assay; Glial Cell Line-Derived Neurotrophic Factor; Hemoglobins; Infarction, Middle Cerebral Artery; Ligation; Male; Nerve Growth Factors; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Up-Regulation