Sleep-wake disturbances are both a risk factor and reported morbidity for intracerebral hemorrhage (ICH). ICH begins with a ruptured blood vessel and blood leakage into the parenchyma. In response to initial damage, pathophysiological processes ensue that both exacerbate and repair damage. Inflammation is a hallmark process of ICH, which includes microglia activation and increased cytokine signaling. Due to the dual role of cytokines as inflammatory signaling proteins and sleep regulatory substances (SRSs), we hypothesized that ICH would activate microglia, increase SRSs, and alter sleep-wake patterns following an experimental model of ICH in the mouse. Male mice were randomized to receive an injection of collagenase (ICH; n = 8) or saline (sham; n = 11) in the striatum of the right hemisphere. Sleep-wake activity was recorded for 6 full days after ICH via noninvasive sleep cages. Blood and tissue were collected at 7 days after ICH to quantify pro-inflammatory cytokines/SRSs (IL-1β, TNF-α, IL-6) and microglia deramification by skeleton analysis. There was an overall injury effect on sleep in mice subjected to ICH at the transition from dark (wake) to light (sleep) at 2, 3, 4, 5, and 6 days after ICH compared with shams. Further analysis confirmed that ICH mice had significantly earlier wake offsets at the dark/light transition and more robust circadian patterns of wake behavior than saline control mice. Spatiotemporal skeleton analysis indicated an increase in microglial cell number with a decrease in endpoints per cell (decreased ramification) for the ipsilateral ICH perihematomal region compared with saline control. There were no changes to plasma cytokine levels at 7 days after ICH when comparing each condition. This is the first known study to show changes in sleep-wake patterns after experimental ICH. Elucidation of mechanisms that link sleep, inflammation, and ICH offers new pharmacological opportunities and rehabilitative strategies to improve recovery in stroke patients.

中文翻译：

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小鼠的脑出血改变了睡眠-觉醒模式并激活了小胶质细胞。

觉醒障碍既是危险因素，又是脑出血（ICH）的发病率。ICH开始于血管破裂和血液渗入实质。响应于初始损伤，随后的病理生理过程加剧和修复了损伤。炎症是ICH的标志性过程，包括小胶质细胞活化和细胞因子信号转导增加。由于细胞因子作为炎症信号蛋白和睡眠调节物质（SRS）的双重作用，我们假设ICH将按照小鼠ICH实验模型激活小胶质细胞，增加SRS并改变睡眠-觉醒模式。雄性小鼠随机接受右半球纹状体注射胶原酶（ICH； n = 8）或生理盐水（假手术； n = 11）的注射。ICH后通过无创性睡眠笼记录了整整6天的睡眠唤醒活动。ICH后第7天收集血液和组织，以通过骨架分析量化促炎细胞因子/ SRS（IL-1β，TNF-α，IL-6）和小胶质细胞脱脂。相较于sha鼠，在ICH后第2、3、4、5和6天从黑暗（清醒）到明亮（睡眠）的转变中，患有ICH的小鼠对睡眠产生了总体伤害。进一步的分析证实，与盐水对照小鼠相比，ICH小鼠在暗/亮过渡时具有明显更早的唤醒偏移，并且唤醒行为的昼夜节律模式更强健。时空骨架分析表明，与生理盐水对照相比，同侧ICH周围血肿区域的小胶质细胞数量增加，每个细胞的终点减少（分枝减少）。比较每种情况时，ICH后7天血浆细胞因子水平没有变化。这是第一个显示实验性ICH后睡眠-睡眠模式改变的已知研究。阐明将睡眠，炎症和ICH联系起来的机制，为中风患者的康复提供了新的药理学机会和康复策略。