局灶性大脑皮层梗死后对侧皮质脊髓束纤维重塑的实验研究

The study of spontaneous contralesional corticospinal plasticity after sensorimotor cortical infarction in hypertensive rats

目的观察大鼠一侧运动感觉皮层局灶性梗死后,梗死对侧(健侧)皮质脊髓束(corticospinal tract,CST)的增殖、芽生现象,并探讨其与神经功能改善的关系。方法采用易卒中型肾血管性高血压大鼠行右侧大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO),假手术组仅暴露而不凝闭大脑中动脉,每组6只。两组予脚步错误试验检测神经功能。术后14 d,两组大鼠左侧运动皮层接受生物素葡聚糖胺(biotinylateddextran amine,BDA)注射标记,术后28 d处死取脑及颈髓,观察非标记侧颈髓CST BDA阳性纤维数量及分布。结果 与假手术组相比,MCAO组标记侧CST发出并越过中线、到达非标记侧颈髓灰质BDA阳性纤维数比值明显增加(11.90×10-4±1.46×10-4vs.3.77×10-4±0.73×10-4),且分布范围广泛。高倍镜下可观察到BDA阳性纤维出现结节样膨大的突触样结构、同时表达神经生长相关蛋白43(growth-associated protein 43,GAP-43)。Pearson相关分析显示,MCAO组大鼠神经功能恢复的程度,与其CST芽生纤维数量呈正相关(r=0.88,P<0.05)。结论 实验性局灶性运动感觉皮层梗死后,诱发健侧CST增殖、芽生发出新纤维越过中线到达对侧颈髓灰质区,可能重建了皮层上运动神经元与脊髓前脚灰质下运动神经元之间的联系,并参与大鼠神经功能恢复的过程。

Objective To study the association of spontaneous contralesional corticospinal tract （CST） remodeling and sprouting in the cervical cord with functional recovery following sensorimotor cortical infarction in hypertensive rats. Methods Adult renovascular hypertensive rats were subjected to permanent right middle cerebral artery occlusion （MCAO）, the sham-operation group underwent the same operation except electroeoagulation for middle cerebral artery（n= 6/group）. Foot-fault test was carried out to monitor motor functional deficit and recovery. Anterograde tracing with bioti- nylated dextran amine （BDA）injected into the contralesional motor cortex was used to assess axonal sprouting in the up- per spinal cord 14 days after stroke. Animals were sacrificed for examination of corticospinal innervation and the synapses 14 days later. Immunofluorescenee was used to detect co-localization of BDA and GAP-43. Result Compared with sham-operation group, in MCAO group, the ratio of contralesional CST axons projection crossing the midline and axon sprout significantly increased （ 11.90× 10 4±4-1.46× 10-4vs3.77× 10±0.73×10-4） and spread over extensive areas. The sprout-ing fibers formed synaptic bouton-like structures and co-located with GAP-43. A significant correlation （r=0.88） was found between functional behavior and the number of CST sprouting fibers crossing the midline in the cervical cord. Con- lusion Unilateral sensorimotor cortical infarction can induce contralesional CST axonal sprouting and rewiring in the de- nervated gray matter of the cervical cord. This phenomenon may contribute to spontaneous functional recovery after stroke.