Starting mechanism underlying corticospinal tract remodeling in rats with focal cerebral infarction

来源 :Joint Symposium of 2016 International Neural Regeneration Sy | 被引量 : 0次 | 上传用户:liulangdetianya
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  After focal cerebral infarction,corticospinal tract from the cerebral cortex on the healthy side can re-cross the midline to dominate the motor neurons in the anterior horn of the spinal cord and thereby promote the recovery of motor function (Chen et al.,2000).However,the underlying starting mechanism remains poorly understood.In this study,we detected the expression levels of growth-associated protein 43 (GAP-43),a protein related to axonal growth,in the cerebral cortex on the healthy side,and brain-derived neurotrophic factor (BDNF) and GAP-43 expression in the anterior horn of the spinal cord on the denervated side (affected side),and then investigated the starting mechanism underlying corticospinal tract remod-eling in rats subjected to middle cerebral artery occlusion (MCAO).Thirty-two male Sprague-Dawley rats were randomly divided into sham-operated and MCAO groups.In each group,rats were further divided into two subgroups according to different time points after the operation: 1-week and 2-week subgroups.Rat models of focal cerebral infarction were estab-lished by occlusion of the right middle cerebral artery using the modified Zea Longa suture method.Beam walking test scores were more significantly increased with time in the MCAO group than in the sham-operated group (P < 0.01).TTC staining revealed infarction foci in the cortex and subcortex of rats subjected to MCAO.Western blot assay results revealed that at 1 and 2 weeks after surgery,the expression level of GAP-43,a marker of axonal growth (Benowitz and Perrone-Bizzozero,1991;Benowitz and Routtenberg,1997),in the left hemisphere of rats in the MCAO group was significantly greater than that in the sham-operated group.At i week after surgery,GAP-43 expression in the spinal cord on the affected side of rats in the MCAO group was similar to that in the sham-operated group,and at 2 weeks after surgery,GAP-43 expression in the MCAO group was higher than that in the sham-operated group.Immunofluorescence staining and confocal laser scanning microscopy results revealed that at I and 2 weeks after surgery,BDNF expression in the anterior horn of the cervical cord on the affected side of rats from the MCAO group was greater than that in the sham-operated group.After focal cerebral infarction,GAP-43 expression in the anterior horn of the cervical cord on the affected side was increased and motor function recovered to a cer-tain degree,suggesting that axons on the denervated cervical cord grew actively.Up-regulation of GAP-43 expression in the cerebral cortex on the healthy side preceded that on the affected side of cervical cord,which likely promotes axonal growth which supports remodeling of the corticospinal tract in the cerebral cortex on the healthy side.These results suggest that after focal cerebral infarction,high BDNF expression also appeared in the cervical cord on the affected side,which provides bene-ficial microenvironment for oriented growth of corticospinal tract at the cervical cord level.This is likely to be a key starting mechanism underlying corticospinal tract remodeling in MCAO rats and it is also an important reason why corticospinal tract remodeling mainly localizes at C4-6 level (Liu et al.,2008).
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