Disturbance of cholinergic pathway after cerebral hemorrhage and its therapeutic strtategy

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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.