[Show abstract][Hide abstract] ABSTRACT: Background:
Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM.
Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs). Further, in an animal study, chronic cerebral hypoperfusion model rats were analyzed for the expression of SDF-1 and HIF-1. CXCR4 antagonist, AMD3100, was also used to detect its effects on cerebral vasculogenesis and SDF-1 expression.
Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression. Cerebral AVM patients also had higher level of EPCs and SDF-1. In chronic cerebral hypoperfusion rats, SDF-1, HIF-1, and CD45 expressions were elevated. The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls.
The SDF-1/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in cerebral AVM lesions, possibly via the recruitment of bone marrow EPCs.
[Show abstract][Hide abstract] ABSTRACT: Tight junctions (TJs) are the most important structure of the blood-brain barrier (BBB). Studies have shown that triggering of white matter lesions (WMLs) may be related to a BBB dysfunction, but rarely have studies observed the progressive changes in TJs longitudinally. In our present study, the ultrastructure of TJs was observed using a transmission electron microscope in Stroke-prone Renalvascular Hypertensive Rats. Western blotting was used to detect TJ-related proteins zonula occludens-1 and occludin. The results showed that in Stroke-prone Renalvascular Hypertensive Rats, the severity of WMLs increased gradually. TJs was destroyed gradually 8 weeks after hypertension. The levels of zonula occludens-1 and occludin also decreased gradually. These data suggested that long-term hypertension may contribute toward the gradual disruption of TJs of BBB and induce WMLs in chronic hypertensive rats.
[Show abstract][Hide abstract] ABSTRACT: To investigate the patient satisfaction with medications commonly used for migraine therapy in patients seen in headache clinic in China with emphasis on the evaluation of Chinese patent medicine (CPM) in relieving acute migraine attack.
Patients admitted at headache clinics in the neurological departments of four hospitals during April to October 2011 were enrolled in the investigation. The questionnaire was designed based on the validation of a diagnostic questionnaire for a population-based survey in China in 2009.
Among 219 eligible patients, 58% had used CPM at the acute attack of migraine while the guideline-recommended treatments were seldom used. However, patients using CPMs were less satisfied than those using Western Medicines (WMs) in either single medication groups or mixed medication groups (P < 0.05).
Fifty-eight percent of the eligible respondents in Guangdong and Guangxi Province had used CPM at the acute attack of migraine, but based on our data, the effect of CPM on treating migraine attack was poor with low satisfaction compared with WMs. However, many factors may bias or explain our findings. This suggests the need for accelerated research in understanding patient choice, treatment availability, and use of medications.
[Show abstract][Hide abstract] ABSTRACT: Pleiotrophin (PTN) is an effective neuroprotective factor and its expression is strikingly increased in microglia after ischemia/reperfusion injury. However, whether PTN could provide neurotrophic support to neurons by regulating microglia function is not clear. In this study, we demonstrated that the expression of PTN was induced in microglia after oxygen-glucose deprivation/reperfusion. PTN promoted the proliferation of microglia by enhancing the G1 to S phase transition. PTN also stimulated the secretion of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and nerve growth factor (NGF) in microglia, but did not upregulate the expression of proinflammatory factors such as TNF-α, IL-1β and iNOS. Mechanistically, we found that PTN increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in microglia in both concentration-dependent and time-dependent manners. In addition, ERK1/2 inhibitor U0126 abolished the proliferation and G1 to S phase transition of microglia stimulated by PTN, and inhibited the production of BDNF, CNTF and NGF induced by PTN. In conclusion, our results demonstrated that PTN-ERK1/2 pathway plays important role in regulating microglia growth and secretion of neurotrophic factors. These findings provide new insight into the neuroprotective role of PTN and suggest that PTN is a new target for therapeutic intervention of stroke.
No preview · Article · Dec 2012 · Neuroscience Research
[Show abstract][Hide abstract] ABSTRACT: Preconditioning-induced cellular adaptation is a new therapeutic strategy for ischemic stroke. This research aims to examine the role of peroxisome proliferator activated receptor (PPAR)-γ co-activator 1-α (PGC-1α) and hypoxia induced factor-1α (HIF-1α) in hypoxic preconditioning-induced protection. In this study, rat artery endothelial cells and neuronal PC12 cells were preconditioned with hypoxia before oxygen-glucose deprivation (OGD) insult. Cell viability, protein expression and oxidative stress were then evaluated. PGC-1α and HIF-1α were knocked down by RNA interference. We found that hypoxic preconditioning significantly reduced cell damage, enhanced the expression of PGC-1α, HIF-1α and VEGF and attenuated oxidative stress in endothelial and PC12 cells in OGD model. The protective effects of hypoxic preconditioning were hardly detected in HIF-1α or PGC-1α deficit cells. The loss of protection was accompanied with a significant loss of VEGF expression in HIF-1α or PGC-1α deficit PC12 cells and PGC-1α deficit endothelial cells as well as a considerable decrease of anti-oxidative effects in PGC-1α knocked-down endothelial cells. The present study demonstrated that both PGC-1α and HIF-1α played crucial roles in hypoxic preconditioning in endothelial and neuronal cells.
[Show abstract][Hide abstract] ABSTRACT: DL-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Recently, we found that NBP can reduce the incidence of stroke and have protective action on cerebral microvessels, suggesting a direct action of NBP on endothelial cells. However, it is difficult to evaluate the direct action of NBP on endothelial cells in vivo because of the interactions of endothelial cells with other types of neuronal cells. Therefore, we investigated whether NBP protects against oxygen glucose deprivation (OGD)-induced cell injury in an immortalized human umbilical vein endothelial cells (HUVEC) in vitro. Cells were exposed to OGD, leading to endothelial damage. Endothelial injury was assessed by measuring MTT and the changes in chromatin morphology. Mitochondrial superoxide, mitochondrial membrane potential and mitochondrial morphology were assessed using MitoSOX Red. Rhodamine 123 and MitoTracker, respectively. Nitrosative stress was assessed by measuring the production of peroxynitrite. The activity of superoxide dismutase (SOD) is evaluated using SOD assay kit-WST. The expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was assessed at the protein level by immunofluorescence and Western blotting. NBP at doses between 0.01 and 100 micromol/L dose-dependently protected against OGD-induced cell death. In addition, NBP attenuated OGD-induced mitochondria superoxide, cellular formation of peroxynitrite, and decrease in SOD activity, mitochondria fragmentation and loss of mitochondrial membrane potential. In parallel, NBP enhanced OGD-induced HIF-1alpha expression. This study demonstrates that NBP can protect HUVEC against OGD-induced oxidative/nitrosative stress, mitochondrial damage and subsequent cell death. This protective effect is, at least in part, associated with its enhancement on OGD-induced HIF-1alpha expression.