Disturbance of cholinergic pathway after cerebral hemorrhage and its therapeutic strtategy

目的：为了解皮质下卒中(脑出血或皮质下梗塞)后神经元网络的紊乱，我们研究了实验性皮质下梗塞和皮质下包块损毁后胆碱能系统的变化。方法：对大鼠皮质下梗塞或皮质下肿块损伤后7天、3个月和12个月的高敏感性乙酰胆碱酯酶(AChE)组织化学进行定量检测。用单侧大脑中动脉(MCA)闭塞的方法造成皮质下梗塞。微球插入和充气造成皮质下肿块损害。免疫组织化学研究还确定胆碱能神经元的变化、胶质反应和脑水肿的程度。我们通过2-脱氧葡萄糖放射自显影来评估皮质下损伤后的神经功能变化。脱氧葡萄糖放射自显影是在生理刺激或没有特定刺激的情况下进行的。结果：假手术组大鼠额叶皮质AChE阳性纤维约为10m/mm~3。皮质下损害导致同侧皮质内AChE阳性纤维明显丢失。皮质下损伤后1周，额叶皮质AChE阳性纤维变为2m/mm~3。皮质下损伤后3个月，额叶皮质AChE阳性纤维略有恢复至3m/mm~3。在皮质下损伤后12个月，我们没有发现进一步的恢复。刺激过程中的脱氧葡萄糖放射自显影显示皮质下损伤后1周皮质激活紊乱。皮质下损毁后3个月，体感皮层活动恢复正常。评论：本研究从形态上揭示了皮质下病变引起的神经功能障碍。在慢性期，我们注意到功能和纤维神经支配的恢复趋势。

Purpose : We studied the changes in the cholinergic system after experimental subcortical infarction and subcortical mass lesion to understand neuronal network disturbances following subcortical stroke (cerebral hemorrhage or subcortical infarction). Methods : We quantitatively evaluated the highly sensitive acetylcholinesterase (AChE) histochemistry 7 days, 3 months, and 12 months after subcortical infarction or subcortical mass lesion in rats. Subcortical infarction was induced by a single middle cerebral artery (MCA) occlusion. Subcortical mass lesion was induced by insertion and inflation of microballoon. Immunohistochemistry was also studied to determine the changes in cholinergic neurons, glial response, and extent of brain edema. We evaluated neurofunctional changes after subcortical lesion by [^<14>C] 2-deoxyglucose autoradiography. Deoxyglucose autoradiography was performed during physiological stimulation of the right face or without specific stimulation. Results : In sham operated rats, quantitative evaluation of AChE histochemistry showed approximately 10m/mm^3 frontal cortex AChE positive fibers. Subcortical lesion resulted in significant loss of AChE positive fibers in the ipsilateral cortex. One week after subcortical lesion, AChE positive fiber became 2 m/mm^3 frontal cortex. Three months after subcortical lesion, AChE positive fiber slightly recovered to 3 m/mm^3 frontal cortex. We could not find further recovery 12 months after subcortical lesion. Deoxyglucose autoradiography during stimulation showed disturbances of cortical activation 1 week after subcortical lesion. Three months after subcortical lesion, the activation of somatosensory cortex was recovered. Comments : Present study morphologically revealed neurofunctional disturbances caused by subcortical lesion. We noted a tendency of recovery of function as well as fiber innervation in the chronic stage.