| BackgroundBrain edema plays an important role after cerebral ischemia and reperfusion injury. Currently, the traditional treatment methods such as high permeability treatment and brain decompression surgery play an important role in the clinical therapy although there is a big limitation in these methods. Many reports have pointed out that aquaporin4is a crucial factor for the formation of brain edema, regulation of AQP4expression after cerebral ischemia has become a target for the treatment of cerebral edema.ObjectiveIn this study, we use magnetic resonance imaging to observe the developing of cerebral edema,aiming to study the impact of pre-exercise on cerebral edema after cerebral ischemia and reperfusion injury.At the same time, we detect its regulation on AQP4protein expression level. to explore the relationship between pre-exercise and cerebral edema from the level of molecular mechanism.MethodsSprague-Dawley male rats were randomly divided into3groups equally:,sham group,pre-exercise group, ischemia group. Rats in exercise group underwent2weeks of treadmill run-training before cerebral ischemia was performed by middle cerebral artery occlusion(MCAO). Rats in ischemia group and sham group conduct2weeks of free movement.Then all rats underwent an MCAO surgery,90mins later,we remove the thread to achieve reperfusion. To detect the process of cerebral edema development at6hour and2days after reperfusion, Diffusion weighted magnetic(DWI) and T2weighted resonance imaging (T2WI) was used. To detect the change of blood brain barrier(BBB) Permeability at6hour and2days after reperfusion, contrast agent injection and post-T1weighted resonance imaging (T1WI) was performed. At the same time, wet and dry weight and evans blue assay were performed at2days after stroke respectively to test the cerebral water content and BBB permeability, Wstern-blot was used to detect AQP4protein expression level of brain from6hour to3day after reperfusion. At two days Garcia score was used to detect the Neurological deficits of all rats.Results1. The cerebral edema results showed that, compared with the sham group, at6h after reperfusion, the rADC of cortical (P<0.05) and striatum (P<0.01) in the ischemic group showed a significant decline, the rADC of cortical (P<0.05) and striatum (P<0.05) in the pre-exercise group also droped. Pre-exercise significantly increased the rADC of the ischemic group at6h after reperfusion in cortex (P<0.05) and striatum (P<0.05). At48h after reperfusion. The rADC of cortex and striatum in the ischemic group elevated compared with6h though with no significant difference (P>0.05). but it is still lower compared with the sham operation group (P<0.05). The rADC of cortex and striatum in the pre-exercise group elevated compared with6h though with no significant difference (P>0.05), and there was no significant difference compared with the sham operation group (P>0.05). There was no significant difference between the pre-exercise group and the ischemic group of the rADC in cortex and striatum (P>0.05). On the ipsilateral cerebral, at6h after reperfusion, the T2values of cortical (P<0.05) and striatum (P<0.05) in the ischemic group increased compared with the sham operation group, there was no significant difference between the pre-exercise group and the sham operation group of the T2values in cortex and striatum (P>0.05), Pre-exercise significantly decreased the T2of the ischemic group at6h after reperfusion in cortex and striatum (P<0.05). At48h after reperfusion, the T2values of cortical (P<0.01) and striatum (P<0.05) in the ischemic group increased compared with the sham operation group, the T2values of cortical (P <0.05) and striatum (P<0.05) in the exercise group also increased compared with the sham operation group. Pre-exercise significantly decreased the T2values of the ischemic group at48h after reperfusion in cortex and striatum (P<0.05). On the contlateral cerebral. There was no significant difference in all the T2values of cortical and striatum (P>0.05). The results of wet and dry weight display,the brain water content of ischemic group increased compared with the sham group at48h after reperfusion (P<0.01), the brain water content of pre-exercise group decreased compared with the ischemic group at48h after reperfusion (P<0.05), and with no significant difference compared with the sham group (P>0.05).2. The change of blood brain barrier(BBB) permeability:On the ipsilateral cerebral.there was no significant difference between the T1signal intensity (T1SIdiff) of pre-exercise group and ischemic group at6h and48h after reperfusion (P>0.05). The PBV of48h after reperfusion in the pre-exercise group and ischemic group increased compared with The PBV of6h(P<0.01).The PBV of pre-exercise group decreased compared with the ischemic group at6h (P<0.05) and48h (P<0.01) after reperfusion. At48h after reperfusion, the T1SIdiff×PBV of pre-exercise group and ischemic group increased compared with The T1SIdiff×PBV of6h (P<0.01). The T1SIdiff×PBV of pre-exercise group decreased compared with the ischemic group at6h (P<0.05) and48h (P<0.01) after reperfusion. On the contlateral cerebral,there was no significant difference in all groups at6h and48h. The results of evans bule content display. On the ipsilateral cerebral, the evans bule content of ischemic group increased compared with the sham group at48h after reperfusion (P<0.01), the evans bule content of the pre-exercese group also increased compared with the sham group (P<0.01). Pre-exercise group decreased the evans bule content compared with the ischemic group (P<0.05), and there was no significant difference in all groups On the contlateral cerebral (P>0.05).3. AQP4protein expression level of brain, compared with the sham group, AQP4protein expression level in the ischemic group increased at6h after reperfusion (P<0.05) and peaked at48h (P<0.01), remained at a high level at72h after reperfusion (P>0.05). AQP4protein expression level in the pre-exercise group increased at6h (P<0.05) and48h(P<0.01) after reperfusion. Pre-exercise can decreased the AQP4protein expression level compared with the ischemic group at6h and48h after reperfusion (P<0.05)。4. The Garcis score at2days after MCAO display, the exercise can reduce the neurological deficits caused by cerebral ischemia in rats, and the difference was statistically significant in the1,3and5item respectively.Conclusion1. Pre-exercise can reduce cerebral edema after cerebral ischemia and reperfusion, this effect may be achieved by down-regulating AQP4expression.2. Pre-exercise can ameliorate the blood-brain barrier damage caused by cerebral ischemia and reperfusion injury. |
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