Department of Psychology and Chemistry of Behavior Program, Texas Christian University, P.O. Box 32878, Fort Worth, TX 76129, USA.
Restor Neurol Neurosci. 1995 Jan 1;8(4):205-12. doi: 10.3233/RNN-1995-8406.
Following brain injury there is an excessive release of excitatory neurotransmitters that may lead to secondary cell death. Although much research has focused on glutamate-NMDA receptor interactions, acetylcholine-muscarinic receptor interactions may also prove to be important for an understanding of the pathophysiological events that lead to secondary degeneration after brain damage. Previous experiments have shown that the muscarinic receptor antagonist scopolamine facilitates recovery from very transient (1 h-10 days) behavioral deficits after fluid percussion injury. The present study extends these findings by investigating whether scopolamine can facilitate recovery from the more enduring behavioral deficits (14-60 days) that follow electrolytic lesions of the rat somatic sensorimotor cortex (SMC). Rats received unilateral lesions of the SMC and a regimen of scopolamine (1 mg/kg) or saline beginning 15 min after surgery. Following SMC lesions rats exhibited an impairment in placing the forelimb contralateral to the lesion as well as an ipsilateral somatosensory asymmetry on a bilateral tactile stimulation test. Rats treated with scopolamine showed a reduction in the initial magnitude of the contralateral placing deficit and an accelerated rate of recovery compared with saline-treated control rats. In contrast, scopolamine had no effect on recovery from the ipsilateral somatosensory asymmetry. These data are consistent with the idea that muscarinic receptor stimulation plays a role in the production of secondary brain damage, that blockade of this receptor leads to a facilitation of recovery on some behavioral tasks, and that electrolytic lesions may trigger some of the same posttraumatic events described in other models of neural trauma.
脑损伤后，兴奋性神经递质过度释放，可能导致继发性细胞死亡。尽管大量研究集中在谷氨酸-NMDA 受体相互作用上，但乙酰胆碱-毒蕈碱受体相互作用对于理解导致脑损伤后继发性退化的病理生理事件也可能证明是重要的。先前的实验表明，毒蕈碱受体拮抗剂东莨菪碱有利于从非常短暂的（1 小时-10 天）流体冲击损伤后行为缺陷中恢复。本研究通过研究东莨菪碱是否能促进大鼠躯体感觉运动皮层（SMC）电解损伤后更持久的行为缺陷（14-60 天）的恢复，扩展了这些发现。大鼠接受单侧 SMC 损伤和东莨菪碱（1mg/kg）或生理盐水治疗方案，从手术后 15 分钟开始。SMC 损伤后，大鼠表现出对损伤侧前肢的放置障碍以及双侧触觉刺激测试中的同侧体感不对称。与生理盐水处理的对照大鼠相比，用东莨菪碱治疗的大鼠表现出对侧放置缺陷初始幅度的降低和恢复速度的加快。相比之下，东莨菪碱对同侧体感不对称的恢复没有影响。这些数据与这样一种观点一致，即毒蕈碱受体刺激在继发性脑损伤的产生中起作用，该受体的阻断导致某些行为任务的恢复得到促进，并且电解损伤可能引发其他神经创伤模型中描述的一些相同的创伤后事件。
