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在大鼠蛛网膜下腔出血模型中,吸入氢气和鞘内注射硫酸镁通过抑制皮层扩散性去极化来改善缺血情况。

Hydrogen inhalation and intrathecal magnesium sulfate ameliorate ischemia by suppressing cortical spreading depolarization in a rat subarachnoid hemorrhage model.

作者信息

Yoshiura Toru, Kawauchi Satoko, Nishida Sho, Sato Sho, Hagita Daichi, Endo Arumu, Nakagawa Masaya, Fujii Takashi, Otsuka Yohei, Mishima Yumiko, Fujii Kazuya, Takeuchi Satoru, Tomiyama Arata, Toyooka Terushige, Sato Shunichi, Wada Kojiro

机构信息

Department of Neurosurgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

出版信息

Neurotherapeutics. 2025 Sep;22(5):e00617. doi: 10.1016/j.neurot.2025.e00617. Epub 2025 May 28.

DOI:10.1016/j.neurot.2025.e00617
PMID:40442014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12491806/
Abstract

This study investigated whether inhaled hydrogen and intrathecal magnesium could mitigate cortical spreading depolarization and delayed cerebral ischemia in a rat model of subarachnoid hemorrhage. Adult male rats underwent subarachnoid hemorrhage induction with nitric oxide synthase inhibition and high-potassium application to elicit cortical spreading depolarization. Animals were assigned to sham, control, H, Mg, or combined H and Mg treatment groups. We measured direct current potentials, cerebral blood flow, brain water content, bodyweight changes, and neurological outcomes. Compared with controls, the H and Mg groups had significantly reduced total depolarization and hypoperfusion times. The combined treatment produced similar benefits. H alone rapidly shortened depolarization duration, suggesting that it may offer neuroprotection until Mg effects fully manifest. Neither treatment altered physiological parameters, brain water content, bodyweight, or neurological deficits. These findings indicate that H and Mg reduce key pathophysiological processes related to early brain injury and delayed cerebral ischemia following subarachnoid hemorrhage, potentially improving outcomes by minimizing depolarization events and associated ischemia. H therapy may provide early protective effects before Mg exertion.

摘要

本研究调查了吸入氢气和鞘内注射镁是否能减轻蛛网膜下腔出血大鼠模型中的皮层扩散性去极化和延迟性脑缺血。成年雄性大鼠通过一氧化氮合酶抑制和高钾应用诱导蛛网膜下腔出血,以引发皮层扩散性去极化。将动物分为假手术组、对照组、氢气治疗组、镁治疗组或氢气与镁联合治疗组。我们测量了直流电位、脑血流量、脑含水量、体重变化和神经功能结局。与对照组相比,氢气治疗组和镁治疗组的总去极化时间和低灌注时间显著缩短。联合治疗产生了类似的效果。单独使用氢气可迅速缩短去极化持续时间,这表明在镁的作用充分显现之前,氢气可能提供神经保护作用。两种治疗均未改变生理参数、脑含水量、体重或神经功能缺损。这些发现表明,氢气和镁可减少蛛网膜下腔出血后与早期脑损伤和延迟性脑缺血相关的关键病理生理过程,通过减少去极化事件和相关缺血可能改善结局。在镁发挥作用之前,氢气治疗可能提供早期保护作用。

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本文引用的文献

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From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.从扩散性去极化到血脑屏障功能障碍:探索创伤性脑损伤的新诊断和治疗方法。
Nat Rev Neurol. 2024 Jul;20(7):408-425. doi: 10.1038/s41582-024-00973-9. Epub 2024 Jun 17.
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Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.早期氢氧混合气吸入治疗动脉瘤性蛛网膜下腔出血患者(HOMA)的随机对照试验研究方案。
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Spreading depolarization: A phenomenon in the brain.
扩散性去极化:大脑中的一种现象。
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Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage.富氢盐水通过调节实验性蛛网膜下腔出血后内质网应激和自噬减轻早期脑损伤。
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