NAT MED:血脑屏障如何维持?

2017-03-14 wangzhe MedSci原创

已报道内皮G-蛋白偶联受体(GPCR)Gpr124是小鼠胚胎中正常前脑血管生成和BBB功能所必需的,但是该受体在成年动物中的作用是未知的。

血脑屏障是指脑毛细血管壁与神经胶质细胞形成的血浆与脑细胞之间的屏障和由脉络丛形成的血浆和脑脊液之间的屏障,这些屏障能够阻止某些物质(多半是有害的)由血液进入脑组织。血液中多种溶质从脑毛细血管进入脑组织,有难有易;有些很快通过,有些较慢,有些则完全不能通过,这种有选择性的通透现象使人们设想可能有限制溶质透过的某种结构存在,这种结构可使脑组织少受甚至不受循环血液中有害物质的损害,从而保持脑组织内环境的基本稳定,对维持中枢神经系统正常生理状态具有重要的生物学意义。

虽然血脑屏障(BBB)失效是多种中枢神经系统(CNS)病症的病因的中心,但控制BBB功能的内皮受体蛋白质性质尚不明确。

已报道内皮G-蛋白偶联受体(GPCR)Gpr124是小鼠胚胎中正常前脑血管生成和BBB功能所必需的,但是该受体在成年动物中的作用是未知的。本实验中Gpr124条件敲除(CKO)在成年小鼠的内皮不影响稳态BBB的完整性,但导致BBB破坏和小鼠模型中的缺血性卒中和胶质母细胞瘤的微血管出血,并且伴有减少脑血管经典Wnt-β-catenin信号。 Wnt-β-catenin信号的组成性激活能够纠正Gpr124-CKO小鼠的BBB破坏和出血缺陷,恢复内皮基因紧密连接,周围细胞覆盖和细胞外基质缺陷。因此,我们认为Gpr124是在成年小鼠的病理条件下内皮Wnt信号传导和BBB完整性特异性必须的内皮GPCR。该发现暗示Gpr124可以做为BBB中断为特征的CNS疾病的潜在治疗靶标。

原始出处:

David C Corney et al. Gpr124 is essential for blood–brain barrier integrity in central nervous system disease.Nature Medicine (2017) doi:10.1038/nm.4309

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    2017-11-29 liye789132251
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    2017-03-16 卡圣

    好好学习,好文章谢谢分享

    0

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    2017-03-15 卡圣

    学习了,谢谢了

    0

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