Neuroprotective properties of prostaglandin I2 IP receptor in focal cerebral ischemia.
Neuroprotective properties of prostaglandin I2 IP receptor in focal cerebral ischemia.
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DOI：
10.1016/j.neuroscience.2010.06.060
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发表时间：
2010-09-29
期刊：
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;Shah ZA;Maruyama T;Narumiya S;Doré S
我们和其他人已经发现，抑制环氧合酶可能不是限制中风后脑损伤的最佳方法。现在我们正在研究各种前列腺素受体的独特性质，以确定阻断那些介导毒性的受体或刺激那些降低毒性的受体是否会改善神经学结果。本研究采用雄性野生型(WT)和IP受体基因敲除(IP−/−)C57BL/6小鼠，研究了前列腺素I2(PGI2)受体在暂时性和永久性大脑中动脉闭塞(TMCAO)和永久性MCAO(PMCAO)临床前卒中模型中的作用。此外，我们还研究了IP受体激动剂贝拉前列素可能的预防和治疗作用。无论是TMCAO还是pMCAO，IP−/−组小鼠的脑梗塞体积和神经功能缺失评分均显著高于WT组小鼠。有趣的是，在TMCAO前30分钟和治疗后(100μg/kg P.O.)，贝拉前列素预处理(50或100μg/kg P.O.)再灌流2或4.5h可显著降低WT小鼠的神经功能缺失评分和脑梗塞体积。PMCAO后4.5h给予贝拉前列素(100μg/kg，P.O.)也能显著减少WT小鼠的神经功能缺失和脑梗塞体积。总之，这些新的发现首次表明，激活PGI2IP受体可以减轻缺血性中风后的解剖和功能损害。
We and others have identified that inhibition of cyclooxygenase might not be the optimal approach to limiting brain damage after stroke. Now we are investigating the unique properties of the various prostaglandin receptors to determine whether blocking those that mediate toxicity or stimulating those that reduce toxicity will improve neurological outcomes. Here, we determined the respective contribution of the prostaglandin I2 (PGI2) receptor in transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent MCAO (pMCAO) preclinical stroke models by using male wildtype (WT) and IP receptor knockout (IP−/−) C57Bl/6 mice. In addition, we investigated the putative preventive and therapeutic effects of the IP receptor agonist beraprost. The infarct volumes and neurological deficit scores (NDS) were significantly greater in IP−/− than in WT mice after both tMCAO and pMCAO. Interestingly, beraprost pretreatment (50 or 100 μg/kg p.o.) 30 min before tMCAO and post-treatment (100 μg/kg p.o.) at 2 or 4.5 h of reperfusion significantly reduced the neurological deficit score and infarct volume in WT mice. Post-treatment with beraprost (100 μg/kg p.o.) 4.5 h after pMCAO also significantly decreased neurological deficits and infarct volume in WT mice. Together, these novel findings suggest for the first time that PGI2 IP receptor activation can attenuate anatomical and functional damage following ischemic stroke.
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DOI：
10.1080/10739680701833804
发表时间：
2008-07
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Sprague RS;Bowles EA;Hanson MS;DuFaux EA;Sridharan M;Adderley S;Ellsworth ML;Stephenson AH
通讯作者：
Stephenson AH
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：
Saleem, S.;Shah, Z. A.;Dore, S.
通讯作者：
Dore, S.
影响因子：
8.3
作者：
Santhanam AV;Smith LA;Katusic ZS
通讯作者：
Katusic ZS
影响因子：
11.1
作者：
Leira, R.;Rodriguez-Yanez, M.;Castillo, J.
通讯作者：
Castillo, J.