Reduced acute brain injury in PGE2 EP3 receptor-deficient mice after cerebral ischemia.
Reduced acute brain injury in PGE2 EP3 receptor-deficient mice after cerebral ischemia.
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DOI：
10.1016/j.jneuroim.2009.01.015
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发表时间：
2009-03-31
影响因子：
3.3
通讯作者：
Doré S
中科院分区：
文献类型：
--
作者：
Saleem S;Kim YT;Maruyama T;Narumiya S;Doré S
缺血性中风是人类死亡和发病的主要原因之一。在脑缺血和随后发生的中风再灌注期间，所谓的“促炎”前列腺素E2（PGE 2）的产生显著增加。因此，人们对PGE 2受体（EP 1 -4）的不同功能及其对缺血性和炎症性刺激后脑损伤的相对作用越来越感兴趣。在这里，我们解决的贡献，EP 3受体在支配短暂性脑缺血后的早期结果。在小鼠海马切片培养中使用氧-葡萄糖剥夺（OGD）诱导的脑缺血体外模型。对于短暂性缺血，将野生型（WT）和EP 3敲除（EP 3-/-）C57 BL/6雄性小鼠的右侧大脑中动脉（MCA）闭塞90分钟并再灌注48或96小时，之后测定神经行为评分和梗死体积。平均动脉血压，pH值，血气（PaO 2和PaCO 2），脑血流量，体温也被确定之前和缺血和再灌注期间。在EP 3 −/−小鼠的脑切片培养物中，OGD诱导的细胞死亡显著低于WT小鼠。经历短暂缺血的EP 3 −/−小鼠在48 h时的梗死体积显著小于WT小鼠，但这种差异在96 h时并不持续。神经功能评分缺陷与梗死体积相关，但两种基因型之间检测到的生理参数无显着差异。结果进一步支持EP 3受体在促进急性缺血性中风中的作用，但EP 3不太可能是PGE 2长期有害后果的唯一贡献者。
Ischemic stroke is one of the leading causes of mortality and morbidity in humans. During brain ischemia and the subsequent reperfusion that occurs with stroke, the generation of the so-called “proinflammatory” prostaglandin E2 (PGE2) increases significantly. Therefore, interest is growing regarding the differential functions of the individual PGE2 receptors (EP1–4) and their relative contribution to brain damage following ischemic and inflammatory stimuli. Here, we address the contribution of the EP3 receptor in dictating early outcomes after transient cerebral ischemia. An oxygen-glucose deprivation (OGD)-induced in vitro model of brain ischemia was used in mouse hippocampal slice cultures. For transient ischemia, the right middle cerebral artery (MCA) of wildtype (WT) and EP3 knockout (EP3−/−) C57BL/6 male mice was occluded for 90 min and reperfused for 48 or 96 h, after which neurobehavioral scores and infarct volumes were determined. Mean arterial blood pressure, pH, blood gases (PaO2 and PaCO2), cerebral blood flow, and body temperature were also determined before and during ischemia and reperfusion. OGD-induced cell death was significantly lower in brain slice cultures of EP3−/− mice than in those of WT mice. EP3−/− mice that underwent transient ischemia had significantly smaller infarct volumes than did WT mice at 48 h, but this difference was not sustained at 96 h. Neurological score deficits correlated with infarct volume, but no significant differences in the physiological parameters monitored were detected between the two genotypes. The results further support a role for EP3 receptors in contributing to acute ischemic stroke, but EP3 is not likely the sole contributor to the long-term detrimental consequences of PGE2.
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影响因子：
8.3
作者：
Iadecola, C;Gorelick, PB
通讯作者：
Gorelick, PB
影响因子：
3.1
作者：
Candelario-Jalil, E;Slawik, H;Fiebich, BL
通讯作者：
Fiebich, BL
影响因子：
2.9
作者：
Ahmad, AS;Ahmad, M;Doré, S
通讯作者：
Doré, S
影响因子：
3.4
作者：
Ahmad, M;Saleem, S;Doré, S
通讯作者：
Doré, S
影响因子：
3.3
作者：
Ahmad, Muzamil;Ahmad, Abdullah Shafique;Dore, Sylvain
通讯作者：
Dore, Sylvain