Department of Neurosurgery, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.
Department of Radiological, The Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.
Exp Neurol. 2024 Jul;377:114803. doi: 10.1016/j.expneurol.2024.114803. Epub 2024 Apr 26.
Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.
皮质脊髓束（CST）的中断是纹状体脑出血（ICH）后运动障碍的主要因素。先前的研究表明，治疗性低温（HT）可改善 ICH 患者的预后。然而，HT 是否对 CST 完整性有直接的保护作用以及潜在的机制在很大程度上仍不清楚。在这项研究中，我们采用化学遗传学方法选择性地激活视前区双侧热敏神经元，以诱导类似低温的状态。然后，我们评估了 HT 治疗对 ICH 后 CST 完整性和运动功能恢复的影响。我们的结果表明，HT 治疗显著减轻了血肿周围和中脑远隔部位 CST 轴突的轴突变性，最终促进了熟练运动功能的恢复。顺行和逆行示踪显示，HT 治疗在较长时间内保护了 CST 的完整性。在机制上，HT 治疗通过减少氧合血红蛋白处理的原代皮质神经元中线粒体 ROS 积累和改善线粒体膜电位来防止血肿周围变性轴突中的线粒体肿胀，减轻线粒体损伤。作为一个原理证明，我们的研究为 HT 在改善 ICH 后功能恢复方面的应用提供了新的见解。
