Repetitive xenon treatment improves post-stroke sensorimotor and neuropsychiatric dysfunction
Repetitive xenon treatment improves post-stroke sensorimotor and neuropsychiatric dysfunction
复制标题
DOI：
10.1016/j.jad.2022.01.025
复制
发表时间：
2022-01-19
影响因子：
6.6
通讯作者：
Huang, Shao-Ling
中科院分区：
文献类型：
--
作者：
Dandekar, Manoj P.;Yin, Xing;Huang, Shao-Ling
中风是一个改变生活的事件，因为中风幸存者经历了个性、情绪和情绪的变化。我们研究了脂质体中的氙气对中风引起的感觉运动障碍以及焦虑和抑郁样表型的影响。大鼠大脑中动脉闭塞(MCAO)6h后再灌流建立缺血性卒中模型。从缺血后2 h开始多次静脉注射氙脂(6 mg/kg)至6 h(5x)，每日1次，连续3d。接受缺血损伤的大鼠在粘连移除、触觉诱发的前肢放置和转杆试验中表现出感觉运动障碍。在强迫游泳测试中，这些动物进入高架迷宫的次数更少，在开放的手臂上花费的时间也更少，在强迫游泳测试中更多地处于被动模式，这表明损伤后28天和35天分别出现了焦虑和抑郁样行为。重复静脉注射氙气脂质体可以改善这些行为异常(p<；0.05)。肠道微生物组分析(16S核糖体RNA基因测序)显示氙脂体组梭状芽胞杆菌簇XI、XIVA、XVIII和乳杆菌减少，普氏杆菌增多。在所有处理中，没有微生物群落受到主要影响。此外，氙气治疗组在缺血后第35天血浆IL-6细胞因子水平升高(-5倍)，而IL-1β、IL-4、IL-10、IL-13和MCP-1水平无明显变化。我们的数据强调了在扩大的脑缺血模型中，氙气-脂质体治疗后卒中后脑损伤的安全性、行为恢复和逆转。这些结果表明，这种治疗策略有可能被移植到中风患者身上。
Stroke is a life-changing event as stroke survivors experience changes in personality, emotions and mood. We investigated the effect of xenon gas encapsulated in liposomes on stroke-generated sensorimotor impairments, and anxiety- and depression-like phenotypes. Ischemic stroke was created by the intraluminal middle cerebral artery occlusion (MCAO) for 6 h followed by reperfusion in rats. Xenon-liposome (6 mg/kg, intravenous) treatment was given multiple times starting at 2 h post-ischemia through 6 h (5X), and once-daily for next 3 days. Rats underwent ischemic injury displayed sensorimotor deficits in the adhesive removal, vibrissae-evoked forelimb placement and rotarod tests. These animals also made lesser entries and spent less time on open arms of the elevated-plus maze and swam more in passive mode in the forced swimming test, indicating anxietyand depression-like behaviors at 28- and 35-days post-injury, respectively. Repeated intravenous treatment with xenon-liposomes ameliorated these behavioral aberrations (p < 0.05). Gut microbiome analysis (16S ribosomalRNA gene sequencing) showed a decrease in the Clostridium clusters XI, XIVa, XVIII and Lactobacillus bacterium, and increase of the Prevotella in the xenon-liposome group. No microbiota communities were majorly affected across the treatments. Moreover, xenon treatment group showed augmented plasma levels of IL-6 cytokines (-5 fold) on day-35 post-ischemia, while no change was noticed in the IL-1 beta, IL-4, IL-10, IL-13 and MCP-1 levels. Our data highlights the safety, behavioral recovery and reversal of post-stroke brain injury following xenon-liposome treatment in an extended ischemic model. These results show the potential for this treatment strategy to be translated to patients with stroke.