The Effect Of Different Rehabilitation Therapies On Functional Recovery After Ischemic Brain Injury In Mice

Background and purpose Experimental studies suggest that bone marrow stromal cells(MSCs)and enriched environment facilitate the improvement of neurological outcomes and promotion of rehabilitation.However,therapeutic effects of MSCs are limited by the number of survival cells.Studies have shown that MSCs transplantation combined with exercise training benefit MSCs survival in the cerebral ischemic region and have a better therapeutic effect.In present study,we explored the therapeutic effect of enriched environment or the combination of MSCs and exercise training on the recovery of motor and social function after ischemic brain injury in mice and study the influences of different rehabilitation therapies on the functional recovery after cerebral ischemia.Methods Thirty-two adult male ICR mice underwent middle cerebral artery occlusion(MCAO).Mice in enriched environment treated group were put into an enriched environment on the first day after middle cerebral artery occlusion(MCAO).Mice in the standard condition treated group were fed in the standard environment.MSCs combined with exercise training group received stereotactic injection of MSCs(4X10~4/μl)in the ischemic surrounding area immediately after MCAO,and started exercise training one day after MCAO.The experiment has four groups:MSC treated group,PBS treated group,MSCs and exercise treated group,and PBS and exercise treated group.The motor function and social behavior of all experimental mice were tested by smart cage,rotarod test and modified neurological severity score(m NSS)on day 7,14,21,28.Results General move test,the occupancy time in the middle of the experimental device,travel,and velocity in the combination of MSCs and exercise training group were significantly higher than that in the MSCs treated group at day 7(p<0.05);the results of rotarod test and m NSS in the combination of MSCs and exercise training group were better recovery compared to the MSCs treated group at day 28(p<0.05).The travel in the combination of PBS and exercise training group was higher than that in the MSCs treated group at day 28(p<0.05).In the general move test,the occupancy time in the middle of the experimental device of the enriched environment treated group were significantly longer than that in the standard environment treated group during the 7 to28 day(p<0.05).In social behavior test,there was a trend of being more interested in strange mice of enriched environment treated group than that in the standard environment treated group,but not statistical significance(p>0.05).Although enriched environment treated group did not stay long enough in the area of strange mice,the occupancy time in the middle of the experimental device of enriched environment treated group were significantly longer than that in the standard environment treated group at day 14,21,and28(p<0.01),and the velocity at the day14 was significantly higher than that in the standard environment treated group(p<0.05),suggesting that the faster recovery of motor function of enriched environment treated group after day 14 may cover up the recovery social behavior function.Conclusions–MSCs therapy or enriched environment therapy could promote neurological function recovery after ischemic brain injury in mice,the combination of MSCs and exercise could achieve better results.