5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage.
5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage.
复制标题
PO/AH 区 5-HT1a 激活诱导脑出血大鼠模型治疗性低温
DOI：
10.18632/oncotarget.20280
复制
发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Hua F
中科院分区：
文献类型：
--
作者：
Liang T;Chen Q;Li Q;Li R;Tang J;Hu R;Zhong J;Ge H;Liu X;Hua F
亚低温治疗作为脑出血的一种神经保护措施被广泛应用。然而，近年来，由于物理低温的副作用，一些临床试验接连失败。越来越多的证据表明，以下丘脑5-HT 1a为靶点的化学低温有可能下调温度设定点，而不会产生重大副作用。因此，本研究检查了5-HT 1a刺激PO/AH区治疗ICH大鼠的有效性和安全性。首先，分别在ICH患者和大鼠模型中研究头部温度与临床结局之间的关系。第二，应用全细胞膜片和共聚焦显微镜观察5-HT 1a受体在PO/AH区的表达和分布。同时，随后应用全细胞贴片研究5-HT 1a受体参与温度调节。第三，我们比较了传统PH和5-HT 1a激活诱导的脑出血大鼠低温的疗效。我们的数据显示，更严重的血肿周围水肿（PHE）和神经功能缺损与ICH后头部温度升高相关。5-HT 1a受体定位于PO/AH区的温敏神经元上，8-OH-DPAT（5-HT 1a受体激动剂）能显著提高温敏神经元的放电频率。8-OH-DPAT治疗提供了更好的脑温降低而没有戒断反弹，与物理低温相比，其对ICH诱导的神经功能障碍、白色损伤和BBB损伤也表现出上级的神经保护作用。这些结果提示，以PO/AH区5-HT 1a受体为靶点的化学低温治疗脑出血可能成为一种新的治疗手段，为脑出血的低温治疗提供新的突破。
Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia.
登录
查看更多内容
影响因子：
3.1
作者：
Finkelstein, Robert A;Alam, Hasan B
通讯作者：
Alam, Hasan B
影响因子：
4.8
作者：
Choi, Ko-Eun;Hall, Casey L.;Yu, Shan P.
通讯作者：
Yu, Shan P.
影响因子：
8.3
作者：
Jauch, Edward C.;Saver, Jeffrey L.;Yonas, Howard
通讯作者：
Yonas, Howard
影响因子：
4.2
作者：
Olsen, Adam S.;Sozda, Christopher N.;Kline, Anthony E.
通讯作者：
Kline, Anthony E.
影响因子：
158.5
作者：
Marion, DW;Penrod, LE;DeKosky, ST
通讯作者：
DeKosky, ST