Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
World Neurosurg. 2022 Dec;168:e19-e27. doi: 10.1016/j.wneu.2022.07.085. Epub 2022 Sep 3.
Despite the arousal effect of median nerve stimulation (MNS) being well documented in the clinical treatment of coma patients with traumatic brain injury (TBI), the mechanisms underlying the observed effect are still not completely understood. This study aimed to evaluate the protective effects and potential mechanism of MNS in comatose rats with TBI.
A total of 60 rats were randomly divided into 5 groups: the control group, sham-stimulated group, MNS group, orexins receptor type 1 (OX1R) antagonist group, and antagonist control group. The free-fall drop method was used to establish a TBI model. After administrating MNS or OX1R antagonist, consciousness was evaluated. Protein levels in the prefrontal cortex were measured using an enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence.
In the MNS group, tissue damage and consciousness state was markedly improved compared with that in the sham-stimulated group. Administration of the OX1R antagonist attenuated the beneficial effects of MNS in TBI-induced comatose rats. Additionally, MNS also significantly enhanced the expression of orexin-A/OX1R and the activation of Ras guanine nucleotide-releasing factor 1 (RasGRF1).
These data show that MNS exerts its wake-promoting effect by activating the OX1R-RasGRF1 pathway in TBI-induced comatose rats.
尽管正中神经刺激（MNS）在创伤性脑损伤（TBI）昏迷患者的临床治疗中具有明显的唤醒作用，但观察到的这种作用的机制仍不完全清楚。本研究旨在评估 MNS 在 TBI 昏迷大鼠中的保护作用及其潜在机制。
将 60 只大鼠随机分为 5 组：对照组、假刺激组、MNS 组、食欲素受体 1（OX1R）拮抗剂组和拮抗剂对照组。采用自由落体坠落法建立 TBI 模型。给予 MNS 或 OX1R 拮抗剂后，评估意识状态。采用酶联免疫吸附试验、Western blot 和免疫荧光法测量前额叶皮质中的蛋白水平。
与假刺激组相比，MNS 组的组织损伤和意识状态明显改善。给予 OX1R 拮抗剂可减弱 MNS 对 TBI 诱导昏迷大鼠的有益作用。此外，MNS 还显著增强了食欲素-A/OX1R 的表达和 Ras 鸟嘌呤核苷酸释放因子 1（RasGRF1）的激活。
这些数据表明，MNS 通过激活 TBI 诱导昏迷大鼠中的 OX1R-RasGRF1 通路发挥其促醒作用。
