Hypothermia followed by rapid rewarming exacerbates ischemia-induced brain injury and augments inflammatory response in rats.
Hypothermia followed by rapid rewarming exacerbates ischemia-induced brain injury and augments inflammatory response in rats.
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DOI：
10.1016/j.bbrc.2016.04.095
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Shu-zhen Zhu;Yong Gu;Zhou Wu;Yafang Hu;S. Pan
中科院分区：
文献类型：
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作者：
Shu-zhen Zhu;Yong Gu;Zhou Wu;Yafang Hu;S. Pan
低温后缓慢复温对缺血性脑卒中具有神经保护作用。然而，缓慢的复温会导致患者在重症监护病房停留的时间更长，并增加低温并发症的风险。低温后快速复温（HTRR）更为方便；但它会加重大面积脑梗死患者的颅内高压。本研究旨在详细探讨HTRR如何加剧缺血性脑损伤及其潜在机制。大脑中动脉闭塞致短暂性局灶性缺血大鼠采用常温或低温后快速复温处理。观察神经预后、神经损伤、血脑屏障完整性和炎症因子表达。结果表明，3°C/20 min的HTRR使神经功能缺损评分和Longa评分升高，神经元损失增加，血浆神经元特异性烯醇化酶水平升高。快速复温大鼠还表现出Evans蓝色染料外渗、基质金属蛋白酶9水平升高和紧密连接损伤。同时，快速复温大鼠血清白细胞介素-1β、-6、肿瘤坏死因子α、环氧化酶-2显著升高。抗炎药米诺环素抑制htrr诱导的炎症细胞因子升高，改善神经预后。这些结果表明，HTRR显著损害脑卒中患者的神经血管单位和增强促炎反应。
Hypothermia followed by slow rewarming is neuroprotective for ischemic stroke. However, slow rewarming causes patients' longer stay in intensive care unit and increases the risk of hypothermic complications. Hypothermia followed by rapid rewarming (HTRR) is more convenient; but it exacerbates intracranial hypertension for patients with massive hemispheric infarcts. The present study aims to investigate in detail how HTRR exacerbates ischemic brain injury and what are underlying mechanisms. Rats subjected to transient focal ischemia by middle cerebral artery occlusion were treated with normothermia or hypothermia followed by rapid rewarming. Neurological outcome, neuronal injury, blood–brain barrier integrity and expressions of inflammatory cytokines were observed. Results showed that HTRR at a rate of 3 °C/20 min increased both neurological deficit score and Longa score, enhanced the loss of neurons and the plasma level of neuron-specific enolase. Rapid rewarmed rats also displayed increased Evans blue dye extravasation, matrix metalloproteinase 9 level and tight junction impairment. Meanwhile, interleukin-1β, -6, tumor necrosis factor α and cyclooxygenase-2 were markedly elevated in rapid rewarmed rats. Anti-inflammatory agent minocycline suppressed HTRR-induced elevation of inflammatory cytokines and improved neurological outcome. These results indicated that HTRR significantly impaired neurovascular unit and augmented proinflammatory response in stroke.