Aims Diabetes mellitus increases the risk of stroke but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion (MCAO) model of ischemia. Methods Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2-GFP mice). Four weeks later, they were subjected to transient (20 min) MCAO. In vivo blood flow was measured by two-photon laser scanning microscopy (TPLSM) in cerebral arteries, veins and capillaries. Results There was a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice as assessed by TPLSM, yet the regional cerebral blood flow, as assessed by laser-Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation in cerebral tissues indicating disruption of the blood brain barrier and disturbed cognitive potential. Conclusion diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.
BackgroundThe cerebral microvascular occlusion elicits microvascular injury which mimics the different degrees of stroke severity observed in patients, but the mechanisms underlying these embolic injuries are far from understood. The Fas ligand (FasL)-Fas system has been implicated in a number of pathogenic states. Here, we examined the contribution of microglia-derived FasL to brain inflammatory injury, with a focus on the potential to suppress the FasL increase by inhibition of the P2X7-FasL signaling with pharmacological or genetic approaches during ischemia.MethodsThe cerebral microvascular occlusion was induced by microsphere injection in experimental animals. Morphological changes in microglial cells were studied immunohistochemically. The biochemical analyses were used to examine the intracellular changes of P2X7/FasL signaling. The BV-2 cells and primary microglia from mice genetically deficient in P2X7 were used to further establish a linkage between microglia activation and FasL overproduction.ResultsThe FasL expression was continuously elevated and was spatiotemporally related to microglia activation following microsphere embolism. Notably, P2X7 expression concomitantly increased in microglia and presented a distribution pattern that was similar to that of FasL in ED1-positive cells at pathological process of microsphere embolism. Interestingly, FasL generation in cultured microglia cells subjected to oxygen-glucose deprivation-treated neuron-conditioned medium was prevented by the silencing of P2X7. Furthermore, FasL induced the migration of BV-2 microglia, whereas the neutralization of FasL with a blocking antibody was highly effective in inhibiting ischemia-induced microglial mobility. Similar results were observed in primary microglia from wild-type mice or mice genetically deficient in P2X7. Finally, the degrees of FasL overproduction and neuronal death were consistently reduced in P2X7−/− mice compared with wild-type littermates following microsphere embolism insult.ConclusionFasL functions as a key component of an immunoreactive response loop by recruiting microglia to the lesion sites through a P2X7-dependent mechanism. The specific modulation of P2X7/FasL signaling and aberrant microglial activation could provide therapeutic benefits in acute and subacute phase of cerebral microembolic injury.
BackgroundThe surgical approaches to thoracolumbar junction (T12-L1) tuberculosis were controversial. We aimed to compare the safety and efficacy of three different procedures through a multicentre retrospective study.MethodsThe medical records of thoracolumbar junction tuberculosis patients (n = 177) from January 2005 to January 2015 were collected and reviewed. Forty-five patients underwent anterior debridement and instrumented fusion (Group A), 52 underwent anterior combined with posterior debridement and instrumented fusion (Group B) and 80 underwent posterior-only debridement and instrumented fusion (Group C). Patients with neurological deficit were 10 in Group A, 23 in Group B, 36 in Group C. All patients had a standard preoperative and postoperative anti - tuberculous therapy regimen. Clinical outcomes, laboratory indexes and radiological evaluation of the three groups were compared. Operations at each centre were performed by the respective senior medical teams of the six different hospitals.ResultsAll three surgical approaches achieved bone fusion and pain relief. Cases with neurological deficits had different degrees of improvement after surgery. The operative time was 330.2 ± 45.4 min, 408.0 ± 54.3 min, 227.9 ± 58.5 min, and the blood loss was 744.0 ± 193.8 ml, 1134.6 ± 328.2 ml, 349.8 ± 289.4 ml in groups A, B and C respectively.The average loss of correction was 5.5 ± 3.7° in group A, 1.6 ± 1.9° in group B, 1.7 ± 2.2° in group C, and the difference between groups except B vs C were of statistically significant (P < 0.05).ConclusionsFor patients with thoracolumbar junction (T12-L1) tuberculosis, the posterior-only procedure is the better than the anterior-only procedure in the correction of kyphosis and maintenance of spinal stability. The posterior-only procedure is recommended because it achieves the same efficacy as combined procedure with shorter operation time, less blood loss and trauma.
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