Behavioral Recovery And Corticospinal Plasticity In Rats After Cerebral Ischemia-Reperfusion And Treatment With Db-cAMP

Background and objective:Nurological deficit is always left behand after cerebral infarction,which is mainly attributable to the limited regeneration capacity of the central nervous system.At present,a lot of reseach betake to improve nerve cell regeneration capacity and its suppressed surrounding microenvironment .cAMP(cyclic adenosine monophosphate ) have attracted much attention because of its ability to overcome myelin-associated inhibitory factor and promote axonal regeneration.Reseach has shown that cAMP can increase the level ArgⅠ(arginaseⅠ) through the PKA pathway,then improve the level of polyamines,thereby promoting axon regeneration.However,these experiments mostly limited to cell culture experiments,its role in cerebral infarction is not clear.Through this experiment,we intend to complete the following objectives:1. To observe whether db-cAMP could enhance neural plasticy in rats after cerebral ischemia-reperfusion .2. To observe whether db-cAMP could improve behavioral recovery in rats after cerebral ischemia-reperfusion.3. To find out the relationship of neural plasticy and behavioral recovery.4. To observe the influence of db-cAMP on the content of ArgⅠmRNA surrounding the infarcted focus,in order to investigate the mechanism of db-cAMP in post-ischemic stroke on promoting and inhibition factor.Method1. SD rats were first trained by reference to Montoya's staircase test,then the right middle cerebral artery ischemia-reperfusion model was induced according to longa's suture method.2. A successful model was randomly divided into experimental group A(30 rats) and control group B(30 rats),each was divided again into 5 groups that is A1-A5 and B1-B5, accordding the execution time that is after the intervention of 4h, 12h, 24h, 48h and 2 months.There were 10 rats in the group of A5 and B5,5 in the remaining groups.3. Group A received the intracerebroventricular injection of db-cAMP 10μl (100μg / NS 10μl),and group B with normal saline 10μl. 4. RT-PCR technique was used to determined the expression of ArgⅠmRNA .5. Behavioral recovery was quantitated by Montoya's staircase test at 1d,1w,2w,3w,4w,5w and 6w after operation.6. The corticospinal plasticity was determined by BDA neuronal tracer.Result1. Compare to control group ,in the experiment group, ArgⅠmRNA began to increase at 4h after treatment ,kept increasing till 48h(p<0.05).2. Motor function changes:1d after operation,the left forelimb activity capacity is extremely poor in both group,they hardly snatched anything.After 1w,their forelimb function began to improve,and during the next 3 weeks,it improved much more obvious,and the experiment group was much better than the control group.However,in the control group ,the forelimb function of the rats had no longer changed after 4w ,which is very different from the experiment group.In the experiment group ,the forelimb function kept improving till 6w afer operation.6w after operation ,the rats in the experiment group could crawl ball for the quantity 58.50±2.22,for the preoperative level of around 83%;while37.40±1.43 in the control group , for the preoperative level of around 52%.The diffence between the two groups was statistically significant(p<0.05).3. Tracing was used to show that CST (corticospinal tract) in cervical enlargement centralize at dorsal funiculus of spinal cord.Under normal circumstances,there are few midline crossing fibers.Midline crossing fibers in the experiment group (7.9%±1.8%)were increased more than the control group(4.1%±1.1%)(p<0.05),it showed the role of midline crossing fibers originating in the unlesioned sensorimotor cortex during the behavioral recovery after cerebral ischemia.The results indicated that db-c AMP promoted and sustained CST axonal sprouting in the cervical enlargement of the spinal cord.Conclusiondb-cAMP can promote the behavioral recovery and the improvement of the corticospinal plasticity in Rats after Cerebral Ischemia-reperfusion .These effects maybe achieve by upregulation of ArgⅠ.