胆碱能神经元活性在蛛网膜下腔出血后即刻意识障碍中的作用机制研究

Loss of conciousness at onset of subarachnoid hemorrhage (SAH) is closely related to poor clinical prognosis, however, the specific mechanisms have not been well elucidated. We previously found that cortical slow waves, which represent unconsciousness, appeared instantly in a near-sober rat SAH model, and the sub-cortical structures played a key role in neocortical slow waves and function inhibition. Meanwhile, cortical neurons with reduced single unit activity (SUA) were choline-positive. Accordingly, based on the latest international research, we speculate that the sudden SAH stimulation can immediately spread to sub-cortical inhibitory structures, resulting in decreased activity of cholinergic neurons, thereby causing neocortex function inhibition, and eventually resulting in loss of consciousness at onset of SAH. In this study, we are aiming at ascending reticular activing system (ARAS) to investigate the specific mechanisms of cholinergic neurons activity in loss of consciousness at onset of SAH, using electrophysiological detection, SUA recording with choline immunofluorescence and choline amperometry in a near-sober rat SAH model. From this research, we expect to better understand the specific pattern of ARAS and mechanisms of unconsciousness at onset of SAH, thereby providing a novel target for early clinical intervention following SAH, and laying the theoretical foundation.

蛛网膜下腔出血（SAH）后即刻意识障碍与临床较差预后密切相关，但目前对其具体机制认识甚微。我们前期研究发现大鼠近清醒SAH模型中可即刻出现代表意识障碍的皮层慢波，且皮层下结构在新皮层功能抑制和新皮层慢波中发挥着重要作用，同时皮层单细胞电活动减少的神经元胆碱复染阳性。结合国际最新研究，我们推测SAH后瞬间形成的蛛网膜下腔血液刺激可即刻播散至皮层下抑制核团，致胆碱能神经元活性下降，从而造成新皮层功能抑制，最终导致SAH后即刻意识障碍。本课题拟通过近清醒大鼠SAH模型，针对网状上行激活系统中胆碱水平，运用神经电生理、单细胞电活动检测、胆碱免疫染色及胆碱电信号检测技术，探讨胆碱能神经元活性在SAH后即刻意识障碍中的具体作用机制。通过此项研究，将有助于深入理解SAH后即刻意识障碍的潜在机制及网状上行激活系统的运行模式，为SAH后早期临床干预提供新的靶点，并奠定理论基础。

蛛网膜下腔出血（SAH）后即刻意识障碍与临床较差预后密切相关，但目前对其具体机制认识甚微。我们前期研究发现大鼠近清醒SAH模型中可即刻出现代表意识障碍的皮层慢波，且皮层下结构在新皮层功能抑制和新皮层慢波中发挥着重要作用，同时皮层单细胞电活动减少的神经元胆碱复染阳性。结合国际最新研究，我们提出假说：SAH后瞬间形成的蛛网膜下腔血液刺激可即刻播散至皮层下抑制核团，致胆碱能神经元活性下降，从而造成新皮层功能抑制，最终导致SAH后即刻意识障碍。本课题通过近清醒大鼠SAH模型，针对网状上行激活系统中胆碱水平，运用神经电生理、单细胞电活动检测、胆碱免疫染色及胆碱电信号检测技术，探讨胆碱能神经元活性在SAH后即刻意识障碍中的具体作用机制。实验结果发现：大鼠SAH后即刻出现频率1-2Hz的皮层慢波，并与大鼠的意识障碍时程保持一致。同时，伴随皮层慢波的出现，额叶皮层中胆碱定量水平显著降低，并且神经电活动显著减少的神经元胆碱免疫阳性。提示胆碱能神经元活性下降可能在SAH后即刻意识障碍中发挥着至关重要的作用。此项研究发现将有助于深入理解SAH后即刻意识障碍的潜在机制及网状上行激活系统的运行模式，为SAH后早期临床干预提供新的靶点，并奠定理论基础。