Effects Of Intensive Training On The Neural Plasticity After Cerebral Ischemia-reperfusion In Rats And Functional Recovery In Stroke Patients

BackgroundStroke is one of the global diseases that severely impair human health.It features high morbidity,high mortality,high disability rate and high rate of recurrent.Among all,ischemic stroke has the largest percentage.It has been found in clinical practice that 2/3 of the patients who were diagnosed of stroke have survived;however,1/2 out of these patients have experienced different degrees of physical dysfunction.This seriously affects the quality of patients' life and working performance,brings a tremendous burden to not only themselves,but also their family.The improvement of quality of life for stroke patients is more and more an important today.Rehabilitation therapy is the major method for the functional recovery of the patients.The mechanism is that the Exercise training can improve the plasticity of central nervous system and functional reorganization;task-oriented exercise training can lead to the proper reorganization of brain function.Exercise training is a common rehabilitation treatment for stroke in clinical practice,which can promote the recovery of ischemic stroke.It has received great attention from experimental and clinical studies.It can promote the recovery of neurological function of damaged brain.Researches indicate that the process of cerebral ischemic can be influenced by exercise training in various ways,including the influence on neuron,neuroglia cells and the apoptosis of nerve cells,etc.Although,more and more studies have confirmed the importance of Exercise training,the optimal intensites of traning is yet to be studied.After the injury of the central nervous system,the synaptic regeneration,neuronal growth and synaptic morphology are all changed,functional training can promote the changes of central nervous plasticity and functional remodeling.At present,most of the brain neural plasticity methods use local transcranial magnetic stimulation and cortical micro-electrode stimulation,through the observation of functional magnetic resonance image results,motor evoked potential and steady-state motor cortical potential changes,less from the morphological perspective and involved in cellular and molecular level to study the role of Exercise training on neural plasticity after ischemic injury and related mechanisms.Objective:This article trys to explore the possible mechanisms of motor training which improves the motor function of rats after cerebral ischemia-reperfusion(CIR)and the effect of intensive training to neural plasticity and apoptosis of rats after CIR.We also try to explore the effects of different intensities of arm training on the functional recovery of hemiplegic upper extremity.We hope to make serial experimental and clinical studies for providing guidance about the motor training intensities for stroke patients.Methods:1.Experimental studies:The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established by inserting a thread into the middle cerebral artery of Sprague Dawley(SD)rats,and randomly dividing into the control group and training groups for different training intensities.All the rats in various groups were further randomly divided into three sub-groups for different postoperative time points(3,7,and 14 days after operation).Training intensities for different training groups were:Group 1:1 training session per day,5 minutes per training session;Group 2:1 training session per day,10 minutes per training session;Groups 3:2 training sessions per day,10 minutes per training session.The rats in the control group and sham operation group were not involved in any treatment interventions until the end of the experiment.We measured the cerebral infarct volume by TTC staining and the structure of neurocyte was observed by Hematoxylin-Eosin(HE)staining.The expression of Sema3A and NRP-1 were analyzed using immunohistochemistry(IHC),RT-PCR,and Western blotting methods respectively.We applied TUNEL stain method to evaluated the apoptosis in peri-infarct cortex.2.Clinical study:Thirty stroke patients were randomly divided into three groups:group A,group B and group C.They were all keeping with enrolling criterion.Patients were received the regular rehabilitation tranining for upper limb for 1 hour(group A),2 hours(group B)and 3 hours(group C)a day respectively,five days per week,for a period of 6 weeks.Motor function was assessed by FMA and ARAT that were carried out before their treatment,two-weeks,four-weeks and six-weeks after traning,Results:Experimental studies:? Effects of intensive training on the motor function,infarct volume and pathology change after cerebral ischemia-reperfusion in rats:The sham group showed normal neurobehavioral functions.There was significant difference between the Garcia NDFS of the control group and that of the sham group(P<0.01);Compared with the control group,the NDFS in training group 1 and 2 at the 3rd day after swimming training showed no significant difference(P>0.05);The Garcia NDFS of the training groups on the 7th and 14th days were significantly higher than that of the control group(P<0.01),especially in the training group 3.At the 3rd,7th and 14th day after swimming training in training group 3,the Garcia NDFS was(12.80±0.45),(15.20±0.45),(16.80±0.45)respectively.The infarction volume in traing group rats was significantly smaller than those in the control group(P<0.01);At the 3rd,7th and 14th day after swimming training in training group 3,the infarction volume was(44.12±0.65),(13.90±1.64),(10.84±1.69)respectively,which was significantly smaller than the infarction volume of the other training groups(P<0.01).The neurocyte of sham group did not have obvious structural and morphologic changes.Compared with the control group,the neuronal damage degrees in all training groups at the 3rd day after swimming training showed no significant difference,while the damage degrees of training group were lower than that of control group at the 7th and 14th day after swimming training,especially the training group 3.? The expression of Semaphorin 3A and Neuropilin-1 in cerebral ischemia-reperfusion rats after intensive training:The Sema3A and NRP-1 expression after MCAO/R were observed in all groups.The Sema3A and NP-1 expressions were mostly higher in peri-infarct cortex in all groups at 3rd day time point.At all the time points,the Sema3A and NP-1 expressions were significantly lower in than those of the control group(P<0.05),the mostly lower expressions was found in group 3(intensive training group).? Effects of intensive training on the apoptosis of neurocytes after cerebral ischemia-reperfusion in rats:TUNEL positive cells are few in sham group.And in control group,the apoptosis rate was(0.4385±0.0227),(0.3012±0.0188),(0.2773±0.0180)respectively at the 3rd,7th and 14th day,TUNEL positive cells was significantly increased compared with the sham group(P<0.01).The number of TUNEL positive cells in all training groups were lower than that of the control group(P<0.01).At the 3rd,7th and 14th day after swimming training in training group3,the apoptosis rate was(0.2943±0.0138),(0.2230±0.0121),(0.1758±0.0170)respectively,the expression of TUNEL positive cells in training group3 was significantly lower than the other training groups(P<0.01).2.Clinical study:Effects of Intensity of Arm Training on Hemiplegic Upper Extremity Motor Recovery in Stroke Patients:The FMA scores of the three groups after six weeks of treatment were(13.00± 6.38),(19.70±7.09),(24.50± 7.96)and the ARAt scores of the three groups were(5.300±3.40),(8.70±4.62),(10.90±3.60).In each group,FMA and ARAT scores increased significantly after six weeks of treatment(P<0.05).When comparing the three groups,there were no many differences between FMA/ARAT after 2 weeks(P>0.05).The FMA scores were(20.50±7.84)in group C,and its improvement were more significant than that in group A(11.90±6.52)and group B(13.80±6.41)after four weeks of treatment(P<0.05);The FMA differences between group A and group B were no significant(P>0.05);The ARAT score improvement were more significant in group C(7.30±2.95)than that in group A(3.30±2.91)(P<0.05);The ARAT differences between group A and group B and group B and group C were not significant(P>0.05).After six week's training,the FMA and ARAT score in group C and group B were improving significant than in group A(P<0.05);There were no many differences in FMA and ARAT score between group B and group C(P>0.05).Conclusions:? Exercise training can reduce the infarct volume after cerebral ischemia-reperfusion in rats and can improve recovery of motor function,the effects of intensive training was more obvious;? Exercise training can inhibit the MCAO-induced Sema3A and NRP-1 expression,and accelerate the neural plasticity of the rats after cerebral ischemia-reperfusion,the effects of intensive training was more obvious;? Exercise training can decrease the induction of apoptosis follow cerebral ischemia-reperfusion in rats,so that has neuroprotective effect,and the effect of intensive training was more obvious.?In clinical study,intensive training can improve the recovery of upper limb motor function in patients with stroke.BackgroundStroke is one of the global diseases that severely impair human health.It features high morbidity,high mortality,high disability rate and high rate of recurrent.Among all,ischemic stroke has the largest percentage.It has been found in clinical practice that 2/3 of the patients who were diagnosed of stroke have survived;however,1/2 out of these patients have experienced different degrees of physical dysfunction.This seriously affects the quality of patients'life and working performance,brings a tremendous burden to not only themselves,but also their family.The improvement of quality of life for stroke patients is more and more an important today.Rehabilitation therapy is the major method for the functional recovery of the patients.The mechanism is that the Exercise training can improve the plasticity of central nervous system and functional reorganization;task-oriented exercise training can lead to the proper reorganization of brain function.Exercise training is a common rehabilitation treatment for stroke in clinical practice,which can promote the recovery of ischemic stroke.It has received great attention from experimental and clinical studies.It can promote the recovery of neurological function of damaged brain.Researches indicate that the process of cerebral ischemic can be influenced by exercise training in various ways,including the influence on neuron,neuroglia cells and the apoptosis of nerve cells,etc.Although,more and more studies have confirmed the importance of Exercise training,the optimal intensites of traning is yet to be studied.Objective:To explore the effects of intensive training on the motor function,infarct volume and pathology change after cerebral ischemia-reperfusion in rats.Method:For establishing rat models,we use intraluminal thread method to make the left MCAO for 2 hours.Then reperfusion for 3 days,7 days and 14 days.After the models were made,150 rats were randomly divided into sham group,training groups(group 1,group 2 and group 3),control group.The training groups rats swam at different intensities:Group 1:1 training session per day,5 minutes per training session;Group 2:1 training session per day,10 minutes per training session;Groups 3:2 training sessions per day,10 minutes per training session,while no training in control group and sham group.The recovery of motor function was evaluated by Garcia neurological functional deficit scales(NDFS).We measured the cerebral infarct volume by TTC staining.And the structure of neurocyte was observed by Hematoxylin-Eosin(HE)staining.Result:The sham group showed normal neurobehavioral functions.There was significant difference between the Garcia NDFS of the control group and that of the sham group(P<0.01);Compared with the control group,the NDFS in training group 1 and 2 at the 3rd day after swimming training showed no significant difference(P>0.05);The Garcia NDFS of the training groups on the 7th and 14th days were significantly higher than that of the control group(P<0.01),especially in the training group 3.At the 3rd,7th and 14th day after swimming training in training group 3,the Garcia NDFS was(12.80±0.45),(15.20±0.45),(16.80±0.45)respectively.The infarction volume in traing group rats was significantly smaller than those in the control group(P<0.01);At the 3rd,7th and 14th day after swimming training in training group 3,the infarction volume was(44.12±0.65),(13.90±1.64),(10.84±1.69)respectively,which was significantly smaller than the infarction volume of the other training groups(P<0.01).The neurocyte of sham group did not have obvious structural and morphologic changes.Compared with the control group,the neuronal damage degrees in all training groups at the 3rd day after swimming training showed no significant difference,while the damage degrees of training group were lower than that of control group at the 7th and 14th day after swimming training,especially the training group 3.Conclusion:Exercise training can reduce the infarct volume after cerebral ischemia-reperfusion in rats and can improve recovery of motor function and faciliate plasticity of neurological function and the effects of intensive training was more obvious.Background:Neurocyte necrosis is the major pathophysiological process after middle cerebral artery occlusion(MCAO)and can cause severe and lasting sequelae.Exercise training can potentially promote functional recovery.We used swimming training on rats with cerebral ischemia-reperfusion(CIR)and explore the underlying neuroprotective mechanism.Objective:After the different intensities exercise training on MCAO in rats,we observed the expression of Sema3A and NRP-1,and explored the possible mechanism of intensive training which can promote MCAO rats' motor function recovery.Methods:The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established by inserting a thread into the middle cerebral artery of Sprague Dawley(SD)rats,and randomly dividing into the control group,the sham group and training groups for different training intensities.The training groups rats swam at different intensities:Group 1:1 training session per day,5 minutes per training session;Group 2:1 training session per day,10 minutes per training session;Groups 3:2 training sessions per day,10 minutes per training session.The control group and the sham group received no training.All the rats in various groups were further randomly divided into three sub-groups for different postoperative time points(3,7,and 14 days after operation).The expression of Sema3A and NRP-1 were analyzed using immunohistochemistry(IHC),RT-PCR,and Western blotting methods respectively.Results:The Sema3A and NRP-1 expression after MCAO/R were observed in all groups.The Sema3A and NP-1 expressions were mostly higher in cortical areas around the infaction in all groups at 3rd day time point.At all the time points,the Sema3A and NP-1 expressions were significantly lower in than those of the control group(P<0.05),the mostly lower expressions was found in group 3(intensive training group).Conclusions:Exercise training(especially intensive training)can inhibit the MCAO-induced Sema3A and NRP-1 expression,and accelerate neura plasticity.Objective:To explore the effects of intensive training on the apoptosis of neurocytes in peri-infarct cortex after cerebral ischemia-reperfusion in rats.Method:To establish ischemia-reperfusion rats model,first we used intraluminal thread method to make the left middle cerebral artery occlusion for 2 hours and then reperfusion.After the models were accomplished,seventy-five male Wistar rats were divided into five groups randomly,they were training group1-3,control group and sham group.The training intensities for different training groups were:Group 1:1 training session per day,5 minutes per training session;Group 2:1 training session per day,10 minutes per training session;Groups 3:2 training sessions per day,10 minutes per training session,while rats of the control group and the sham group did no training.We applied TUNEL stain method to evaluated the apoptosis in peri-infarct cortex at the 3rd,7th,14th days after swimming training.Result:TUNEL positive cells are few in sham group.And in control group,the apoptosis rate was(0.4385±0.0227),(0.3012±0.0188),(0.2773±0.0180)respectively at the 3rd,7th and 14th day,TUNEL positive cells was significantly increased compared with the sham group(P<0.01).The number of TUNEL positive cells in all training groups were lower than that of the control group(P<0.01).At the 3rd,7th and 14th day after swimming training in training group3,the apoptosis rate was(0.2943±0.0138),(0.2230±0.0121),(0.1758±0.0170)respectively,the expression of TUNEL positive cells in training group3 was significantly lower than the other training groups(P<0.01).Conclusion:Exercise training can decrease the induction of apoptosis follow cerebral ischemia-reperfusion in rats so that has a neuroprotective effect,and the effect of intensive training is more obvious.Objective:Our study' objective was to discusses the effects of some different intensities of arm Exercise training on the functional recovery of hemiplegic upper extremity.Methods:Thirty stroke patients were randomly divided into three groups:group A,group B,group C.They all keeping with enrolling criterion.All of the patients were received the regular rehabilitation therapy.Each group received upper limb training for 1 hour(group A),2 hours(group B)and 3 hours(group C)a day respectively,five days per week,for a period of 6 weeks.Motor function was assessed by FMA and ARAT that were carried out before their treatment,after two-weeks;after four-weeks and after six-weeks.Results:The FMA scores of the three groups after six weeks of treatment were(13.00 ± 6.38),(19.70±7.09),(24.50±7.96)and the ARAt scores of the three groups were(5.30±3.40),(8.70±4.62),(10.90±3.60).In each group,FMA and ARAT scores increased significantly after six weeks of treatment(P<0.05).When comparing the three groups,there were no many differences between FMA/ARAT after 2 weeks(P>0.05).The FMA scores were(20.50±7.84)in group C,and its improvement were more significant than that in group A(11.90±6.52)and group B(13.80±6.41)after four weeks of treatment(P<0.05);The FMA differences between group A and group B were no significant(P>0.05);The ARAT score improvement were more significant in group C(7.30±2.95)than that in group A(3.30±2.91)(P<0.05);The ARAT differences between group A and group B and group B and group C were not significant(P>0.05).After six week's training,the FMA and ARAT score in group C and group B were improving significant than in group A(P<0.05);There were no many differences in FMA and ARAT score between group B and group C(P>0.05).Conclusion:Increasing in the intensity of arm training could help the motor function recovery upper extremity in stroke patients.