Effects of Noggin-Transfected Neural Stem Cells on Neural Functional Recovery and Underlying Mechanism in Rats with Cerebral Ischemia Reperfusion Injury.

OBJECTIVE: To investigate neuroprotection of noggin-transfected neural stem cells (NSCs) against focal cerebral ischemia reperfusion injury (IRI) in rats. METHODS: Eighty Wistar rats were randomly divided into the sham, IRI, NSCs, and noggin + NSCs groups. Noggin containing adenoviral vectors was transfected into rat NSCs. Rats were subjected to 2.0 hours middle cerebral artery occlusion and reperfusion 1.0 hour, followed by infusion into the lateral ventricles of NSCs alone, noggin-transfected NSCs, and saline at 3 days in the NSCs, noggin + NSCs, and sham groups, respectively. All rats were sacrificed on 1, 3, 7, and 28 days after transplantation; the colorimetric method was used to detect the levels of superoxide dismutase (SOD) and the malondialdehyde (MDA) content after the behavior capability determined. Western blot was performed for detecting the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) proteins. The TUNEL-positive and BrdU/nestin double-positive cells were observed under a light microscope and quantitative analysis was performed by morphometric technique. RESULTS: Noggin-transfected NSCs significantly decreased the infarct volume and improved the neurological scores. Noggin-transfected NSCs also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Noggin-transfected NSC transplantation markedly decreased the MDA levels and increased the SOD activity, and simultaneously downregulated the BMP4 (bone morphogenesis protein), VEGF, and bFGF proteins. CONCLUSIONS: The present study demonstrates that grafting NSCs modified by noggin gene provides better neuroprotection for cerebrovascular disease.

VEGF overexpression in transplanted NSCs promote recovery of neurological function in rats with cerebral ischemia by modulating the Wnt signal transduction pathway.

Neural stem cell transplantation is a good method to treat stroke, but the mechanism is still unclear. Therefore, this study aims to explore the regulatory mechanism of VEGF overexpression in transplanted NSCs to promote the recovery of neural function in ischemic rats by regulating Wnt signal transduction pathways. We amplified VEGF gene fragments by PCR and transfected them into NSCs with Ad5 adenovirus. Rat brain IRI model was established by MCAO method, and VEGF transfected NSCs (VEGF-NSCs) were transplanted 24 h after successful IRI model. One week after the transplant, cognitive function was assessed using a neurological deficit score; Brain injury was assessed by histopathology; Photochemical and ELISA methods were used to detect oxidative stress markers and inflammatory factors, respectively. Western blotting has been detected in molecules of the Wnt signaling pathway. The results showed that the transduced NSCs express VEGF at least for 14 days. VEGF-NSCs transplantation (VNT) improved spatial learning and memory in rats, and inhibited oxidative stress injury, inflammatory response, and histopathological injury. VNT also resulted in significant changes in the phosphorylation levels of ß-catenin and GSK-3ß proteins, ultimately triggering activation of the Wnt signal transduction pathway. These results suggest that the neuroprotective effects of VNT may be related to the regulation of the Wnt signal transduction pathway.

Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

[Anatomical study and three dimensional image characteristic analysis of basicranial artery and its clinical significance].

OBJECTIVE: To observe and measure the inside diameter of basicranial arteries, the angulation of main arteries, the three dimensional image characteristic of internal carotid arteries and the anatomical variation of Willis circle. METHODS: The arteries of 30 formalin-fixed adult heads were injected with latex after which the caliber and characteristic of cerebral arteries were observed and measured. The three dimensional image characteristic of internal carotid arteries and its branches were measured using 3D-DSA. RESULTS: (1) Main artery caliber: origin of internal carotid artery (Left 5.12 +/- 1.48 mm; Right 5.11 +/- 1.42 mm); origin of middle cerebral artery (Left 2.93 +/- 1.44 mm; Right 2.92 +/- 1.46 mm); origin of anterior cerebral artery (Left 2.63 +/- 1.33 mm; Right 2.61 +/- 1.32 mm); origin of vertebral artery (Left 4.37 +/- 1.21 mm; Right 3.22 +/- 1.64 mm); origin of basilar artery (4.45 +/- 1.28 mm); origin of posterior cerebral artery (Left 2.62 +/- 1.36 mm; Right 2.61 +/- 1.22 mm). (2) The angulation of main arteries: C1, 2 of ICA and C4, 5 of ICA (Left 32 +/- 22 degrees; Right 36 +/- 28 degrees ); ICA and ACA (Left 43 +/- 26 degrees; Right 46 +/- 28 degrees). (3) The results show that anatomical and three dimensional image characteristic of internal carotid arteries have no difference (P > 0.05). (4) The anatomical variation of Willis circle: Type O (56.7%); Type A (16.7%); Type P (20.0%); Type AP (6.7%). CONCLUSIONS: It is helpful to measure the inside diameter of basicranial arteries for the selection of various catheter in interventional neuroradiology, to observe the angulation of main arteries and the three dimensional image characteristic of internal carotid arteries for the moulding of various catheter in endovascular therapy and to master the anatomical variation of Willis circle for decreasing complications of endovascular treatment and judging prognosis of cerebrovascular diseases.