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@#Objective:To observe the interactive effects of early exercise and γ-aminobutyric acid (GABA) receptor antagonists on the neurologic function and brain-derived neurotrophic factor (BDNF) expression in the cerebral ischemia-reperfusion (I/R) rat model. Methods:Male Sprague-Dawley rats were divided into sham (<italic>n</italic> = 10), I/R (<italic>n</italic> = 10), exercise (EX) (<italic>n</italic> = 10), pentetrazol (PTZ) (<italic>n</italic> = 10) and pentetrazol plus exercise (PTZEX) (<italic>n</italic> = 10) groups. All the rats, except the sham group, accepted middle cerebral artery occlusion (MCAO) for one hour and reperfused. Since two days after reperfusion, PTZ and PTZEX groups accepted PTZ, a GABA receptor antagonist, 0.25 mg/kg peritoneal injection, once a day for five days; while EX and PTZEX groups ran on a treadmill, 30 minutes a day for five days. Seven days after reperfusion, all the rats were assessed with neurobehavioral score, the infarct volumes were assessed with TTC, and BDNF expression in ischemic penumbra was detected with reverse transcription polymerase chain reaction and ELISA. Results:Compared with I/R group, the neurobehavioral scores of EX group, PTZ group and PTZEX group improved, the volumes of cerebral infarction reduced (<italic>P </italic>< 0.05), and PTZEX group was the best (<italic>P </italic>< 0.05). The expression of BNDF was the most in PTZEX group (<italic>P </italic>< 0.05). Conclusion:Early exerxise combined with PTZ could promote the recovery of neurologic function in I/R rats, which may be related to the up-regulation of BDNF.
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Objective To evaluate the effect of inhibition of ubiquitin carboxy terminal hydrolase LI (UCHL1) on cerebral ischemia/reperfusion injury in mice. Methods Male BALB/c mice were randomly divided into sham group, ischemia/reperfusion (I/R) group, UCHL1 small interfering RNA (siRNA)group and scramble siRNA (control) group, 10 mice in each group. I/R model was established by reperfusion 24 hours after middle cerebral artery occlusion (MCAO) 60 minutes. In the siRNA group and control group, 10 JJLI UCHL1 siRNA or scramble siRNA was injected into the brain through the lateral ventricle 24 hours before MCAO. The expression of UCHL1 was detected by RT-PCR and Western blotting; the volume of cerebral infarction and the rate of edema were assessed by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining; and the score of neurological symptoms was assessed by neurobehavioral scoring. Results Compared with the sham group, the level of UCHL1 mRNA and protein in ischemic penumbra of I/R group were significantly higher (P< 0.05), while the expression of UCHL1 protein and mRNA in siRNA group were significantly lower (P< 0.05); at the same time, the volume of cerebral infarction, edema rate and neurobehavioral damage in I/R group increased significantly, while the volume and edema rate of cerebral infarction and neurobehavioral damage in siRNA group further increased (P< 0.05). Conclusion Inhibition of UCHL1 can aggravate the cerebral ischemia/reperfusion injury in mice, suggesting that the induction of UCHL1 after MCAO has a protective effect on the cerebral ischemia/reperfusion injury in mice.
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Objective To investigate the effects of transient receptor potential vanilloid-1 (TRPV1) antagonist AMG517 on cerebral ischemic / reperfusion injury in mice. Methods Forty male C57BL / 6 mice were assigned to the following groups: sham group, vehicle + ischemia / reperfusion group (vehicle), capsaicin + ischemia / reperfusion group (capsaicin), and AMG517 + ischemia / reperfusion group (AMG517) . Ischemic / reperfusion injury was induced by permanent middle cerebral artery occlusion(MCAO) and neurological deficits were evaluated 72 hours after MCAO. Then, infarct volume, brain edema, mRNA expression of TRPV1 and serum concentrations of tumor necrosis factor α(TNF-α) and interleukin-10 (IL-10) were measured. Results Compared with the vehicle group, AMG517 significantly decreased the infarct volume (P < 0. 01) . Neurobehavioral score significantly decreased following administration of AMG517 (P < 0. 01) 72 hours after MCAO. Compared with the sham group, the mRNA expression of TRPV1 significantly increased in vehicle group (P < 0. 01) . AMG517 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P<0. 05) . Conclusion AMG517 can improve ischemia / reperfusion injury in mice and may play a neuroprotective effect by alleviating inflammation.
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Objective To explore the role of microRNA-181b (miR-181b) in cerebral ischemic injury in vivo and its mechanism. Methods Using middle cerebral artery occlusion (MCAO) model to mimic ischemic injury in vivo, the heat shock protein A5(HSPA5) protein level was determined by using Western blotting. The extent of neural cell loss in ischemic cortex after MCAO was assessed by Nissl staining. Neurological score was performed to evaluate the degree of cerebral ischemic injury after MCAO. Results We found that miR-181b antagomir down-regulated miR-181b expression levels in cerebral ischemic cortex of mice after MCA0(P <0.05, n =3). MiR-181 b antagomir improved neurological deficit of mice at 24 hours after transient MCAO (P < 0.05, n =6). HSPA5 protein levels were significantly up-regulated in ischemic cortex of mice after MCAO, and miR-181b antagomir further up-regulated HSPA5 (P < 0.05, n=3). Consequently, miR-181b antagonists attenuated neural cell loss in ischemic cortex after MCAO (P <0.05, n=3). Conclusion MiR-181 b plays an important role in ischemic injury of mice through regulating HSPA5 protein level.
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<p><b>AIM</b>To explore the effects of periphery injection of L-SOP on the activation of p38MAPK in spinal cord in formalin pain model in rats.</p><p><b>METHODS</b>Fourty-eight male Wistar rats were divided randomly into four groups (n=12): NS group and three different dose of L-SOP groups. For each group, 6 rats used to observe flinching and licking time every as nociception behavior 3 minutes in 1 hour after formalin injected and the other 6 rats used to observe the activation of p38(P-p38) by Western blotting.</p><p><b>RESULTS</b>All the three different groups of L-SOP could inhibit nociception behavior in the tonic phase,and 250 nmoVl/L and 500 nmol/L groups could suppress not only in the tonic phase but also in the acute phase. 250 nmol/L and 500 nmol/L groups could reduce activated or phosphorylated p38MAPK in spinal cord.</p><p><b>CONCLUSION</b>Periphery injection of L-SOP can reduce nociceptive behavior and phosphorylated p38MAPK in the spinal cord in formalin-induced hyperalgia, it is suggested that there is functional expression of mGluRs III in the periphery and is involved in the processing of peripheral noxious informations.</p>