The neuroprotection of electro-acupuncture via the PGC-1α/TFAM pathway in transient focal cerebral ischemia rats

ATP depletion is one of the pathological bases in cerebral ischemia.Electro-acupuncture(EA)is widely used in clinical practice for ischemia.However,the mechanism of EA remains unclear.The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and,consequently,increase the preservation of ATP in rats with ischemia.In this study,48 rats were randomly divided into four groups as a sham-operation control group(sham group),a middle cerebral artery occlusion group(MCAO group),an EA group,and an EA group blocked by the AMPK inhibitor compound C(EA+CC group)(N=12/group).The rats of the EA group and EA+CC group received the EA treatment for 7 days.The rats that belonged in the two remaining groups were only grasped in the same condition.Then,their brain tissues were collected for further detection.When compared with other groups,EA significantly reduced neurological deficits score and increased motor function.The cerebral infarction volume was significantly reduced in the EA group according to TTC staining.With western blot,we found that EA improved the ratio of p-AMPKα/AMPKα(P<0.05),however,there is no difference between the MCAO group and sham group(P>0.05).In addition,EA also increased the expression of PGC-1αand TFAM(all P<0.05).By Elisa,we observed that EA increased the preservation of ATP(P<0.05)and mitochondrial respiratory enzymes,including Complex I(P<0.05),Complex IV(P<0.05),but not Complex III(P>0.05).In summary,we conclude that EA may protect against ischemic damage in MCAO rats,improve the preservation of ATP and mitochondrial respiratory enzymes.This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.

Effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury

BACKGROUND： Restraint stress is a typical psychophysiological stressor. Simulating the early passion and difficulty in walking of patients after attack of stroke meets onset features.OBJECTIVE： To evaluate the effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury, and to investigate the feasibility for its being as modeling method of depression model after stroke.DESIGN： A randomized controlled animal experiment.SETTING： Department of Clinical Medicine, Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA.MATERIALS： Forty-eight male Sprague-Dawley rats, weighing 240 - 270 g, provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA were used in the current study.METHODS： The experiments were carried out in the Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA between August 2005 and August 2006. ①Experiment intervention： The rats were randomized into middle cerebral artery occlusion-reperfusion （MCAO） ＋stress group, simple MCAO group, sham-operation ＋ stress group and simple sham-operation group, with 12 rats in each group.Rats in the first two groups were developed into cerebral ischemia/reperfusion models by suture-occluded method. Rats in the MCAO＋stress group were modeled and restraint stress scheme was performed. At week 5 after modeling, the rats were placed in self-made restraining tubes, 2 hours/time, once a day, for 2 successive weeks. The common carotid artery, external and internal carotid arteries of rats in the latter two groups were exposed. The stress way of sham-operation＋ stress group was the same as that of MCAO＋ stress group. ②The neurological status grading and motor performance evaluation （screen test, rota-rod test and balance beam test） were conducted in rats with simple sham-operation group and MCAO group before, 1st and 28^th days after modeling. Depression-like behavior test was performed in the rats of each group by sucrose preference test and open field test at the end of the experiment.MAIN OUTCOME MEASURES： Changes of depression-like behaviors of rats in each group.RESULTS： Forty-eight rats were involved in the experiment. Two rats with meningeal irritation sign were excluded from simple MCAO group, and one rat in the MCAO＋stress group died of some unclear causes during the experiments. The other 45 rats entered the stage of finial analysis. ① Depression-like behavior assessment results： The rats in the MCAO＋ stress group had a significantly decreased preference for sucrose solution, crossing and rearing scores, and increased immobility duration after the 14-day restraint stress,compared with those in other three groups （all P〈0.05）. ②The neurological status grading and motor performance evaluation： There were significant differences in the two indexes of rats in the simple MCAO group before, 1^st and 28^th days after modeling （P〈0.01）, while there was no significant difference before and 28^th days after modeling （P〉0.05）. There were no significant changes in sham-operation group at each time point （P〉0.05）.CONCLUSION： After being exerted restraint stress, the rats with transient focal ischemic injury may show obvious depression-like behaviors. Therefore, restraint stress can be used as a novel animal modeling method for further studying biological mechanism in central nervous system of post-stroke depression animals.