TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke.
TRPV1-mediated Pharmacological Hypothermia Promotes Improved Functional Recovery Following Ischemic Stroke.
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DOI：
10.1038/s41598-017-17548-y
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发表时间：
2017-12-15
影响因子：
4.6
通讯作者：
Marrelli SP
中科院分区：
文献类型：
--
作者：
Cao Z;Balasubramanian A;Pedersen SE;Romero J;Pautler RG;Marrelli SP
低温显示出中风神经保护的前景，但目前的冷却策略会导致不良的副作用，限制其临床应用。越来越多的努力集中在药物低温作为中风的治疗选择。以前，我们表明，激活的温度调节离子通道，瞬时受体电位香草素1（TRPV1），由二氢辣椒素（DHC）产生可靠的低温。在这项研究中，我们研究了TRPV1介导的DHC低温对长期缺血性卒中损伤和功能结局的影响。卒中后3.5小时开始的低温显著减少了原发性皮质损伤。有趣的是，DHC的低温也显著减少了继发性丘脑损伤，因为DHC治疗的中风小鼠表现出53%的丘脑病变大小。通过扩散张量成像（DTI），DHC治疗的中风小鼠进一步证明丘脑中神经元损失和星形胶质细胞增生减少，丘脑纤维损失减少。重要的是，中风后DHC对低体温的单次8小时治疗提供了功能结果的长期改善，因为DHC治疗的小鼠在中风后一个月表现出改善的行为恢复。这些发现表明，TRPV1介导的低温可有效减少原发性皮质损伤和远端继发性丘脑损伤，并且单次治疗可对功能恢复产生持续影响。这些数据突出了TRPV1激动剂用于中风治疗的治疗潜力。
Hypothermia shows promise for stroke neuroprotection, but current cooling strategies cause undesirable side effects that limit their clinical applications. Increasing efforts have focused on pharmacological hypothermia as a treatment option for stroke. Previously, we showed that activation of a thermoregulatory ion channel, transient receptor potential vanilloid 1 (TRPV1), by dihydrocapsaicin (DHC) produces reliable hypothermia. In this study, we investigate the effects of TRPV1-mediated hypothermia by DHC on long-term ischemic stroke injury and functional outcome. Hypothermia initiated at 3.5 hours after stroke significantly reduced primary cortical injury. Interestingly, hypothermia by DHC also significantly reduced secondary thalamic injury, as DHC-treated stroke mice exhibited 53% smaller thalamic lesion size. DHC-treated stroke mice further demonstrated decreased neuronal loss and astrogliosis in the thalamus and less thalamic fiber loss by diffusion tensor imaging (DTI). Importantly, a single 8 hour treatment of hypothermia by DHC after stroke provided long-term improvement in functional outcome, as DHC-treated mice exhibited improved behavioral recovery at one month post-stroke. These findings indicate that TRPV1-mediated hypothermia is effective in reducing both primary cortical injury and remote secondary thalamic injury, and a single treatment can produce persistent effects on functional recovery. These data highlight the therapeutic potential for TRPV1 agonism for stroke treatment.
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影响因子：
3.5
作者：
Lyden, Patrick;Ernstrom, Karin;Hemmen, Thomas
通讯作者：
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DOI：
10.1152/ajpregu.00329.2013
发表时间：
2014-01-01
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