cholecalciferol and Brain-Ischemia

Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R.

Topics: Animals; Brain Ischemia; Cholecalciferol; Disease Models, Animal; Gerbillinae; Male; Matrix Metalloproteinase 9; NADPH Oxidases

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

The aim of this study is to determine the protective effects of vitamin D(3) and dehydroascorbic acid (DHA), a blood-brain barrier transportable form of vitamin C, against ischemia/reperfusion (I/R) injury on a middle cerebral artery occlusion/reperfusion model of brain since reactive oxygen species play an important role in the pathophysiology of I/R injury in brain. In order to examine antioxidant status and lipid peroxidation, we assayed malondialdehyde (MDA) levels as a marker of lipid peroxidation, and reduced glutathione (GSH) and superoxide dismutase (SOD) enzyme activities as free radical scavenging enzymes in cortex and corpus striatum (CS). Wistar albino rats were divided into five equal groups of each consisting of seven rats: control, I/R, I/R + DHA, I/R + vitamin D(3), and I/R + vitamin D(3) + dehydroascorbic acid groups. MDA levels were found to be increased in the I/R group, I/R + DHA, and I/R + vitamin D(3) groups compared with the control group in both cortex and corpus striatum. However, MDA level were found to be significantly decreased in only I/R + vitamin D(3) + DHA group compared with the I/R group in cortex (P < 0.0001). MDA levels were not significantly different in I/R + DHA, and I/R + vitamin D(3) groups compared with the I/R group. GSH and SOD enzyme activities were significantly decreased in I/R, I/R + DHA, and I/R + vitamin D(3) groups compared with the control group in both cortex and corpus striatum (CS) (P < 0.0001). Whereas, both GSH and SOD activity were increased in I/R + vitamin D(3) + DHA group compared with the I/R group in both cortex and CS (P < 0.001 in cortex, P < 0.001 in CS for SOD P < 0.002 in cortex P < 0.03 in CS for GSH). Our results demonstrate that the combination of vitamin D(3) and DHA treatment prevent free radical production and dietary supplementation of vitamin D(3) and DHA which may be useful in the ischemic cerebral vascular diseases.

Topics: Analysis of Variance; Animals; Brain Ischemia; Cerebral Cortex; Cholecalciferol; Corpus Striatum; Dehydroascorbic Acid; Disease Models, Animal; Drug Combinations; Glutathione; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase

This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential

Topics: Animals; Blueberry Plants; Brain Ischemia; Carnosine; Cell Differentiation; Cholecalciferol; Dietary Supplements; Disease Models, Animal; Doublecortin Protein; Drugs, Chinese Herbal; Male; Nervous System Diseases; Neurons; Neuroprotective Agents; Plant Extracts; Rats; Rats, Sprague-Dawley; Stroke; Tea