Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia
Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia
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DOI：
10.1016/j.brainres.2008.02.101
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发表时间：
2008-05-07
期刊：
影响因子：
2.9
通讯作者：
Kemikler, Gonul
中科院分区：
文献类型：
--
作者：
Kaya, Mehmet;Gurses, Candan;Kemikler, Gonul
皮质发育不良(CD)是导致血脑屏障(BBB)障碍致癫痫的主要原因之一。本研究观察了戊四氮(PTZ)点燃镉对大鼠血脑屏障功能和超微结构的影响。E17孕鼠接受145cGy伽玛射线照射，并以仔鼠为实验对象。每周给大鼠注射三次PTZ以诱导点燃。用荧光素钠(NaFlu)测定血脑屏障通透性。用免疫组织化学方法检测阻滞素、GFAP和c-fos的表达，免疫印迹法检测阻滞素的表达，并用电子显微镜观察血脑屏障的超微结构变化。Cd和/或点燃大鼠脑内NaFlu水平未见升高。在给予惊厥剂量的PTZ后，观察到镉点燃的大鼠血脑屏障通透性显著增加。封闭素的免疫反应和表达在所有组中基本保持不变。除对照组外，其余各组GFAP免疫反应均有轻微增强。惊厥激发PTZ后，Cd点燃大鼠脑切片中c-fos免疫反应明显增强。致痫剂量的戊四氮点燃大鼠脑内皮细胞紧密连接的超微结构完整，但吞噬小泡明显增多。本研究表明，在Cd参与的点燃致痫过程中，惊厥刺激PTZ诱发癫痫发作改变了血脑屏障的功能和超微结构，并显著增强了跨内皮泡的转运，而细胞旁通路显然不参与这一过程。(C)2008 Elsevier B.V.所有紧身衣已保留。
Cortical dysplasia (CD) is one of the major causes contributing to epileptogenesis associated with blood-brain-barrier (BBB) disturbances. The current study investigated the functional and ultrastructural changes of BBB in pentylenetetrazole (PTZ)-kindled rats with CD. Pregnant rats on E17 were exposed to 145 cGy of gamma-irradiation and offspring were used for experiments. The rats were given PTZ three times per week to induce kindling. The permeability of BBB was determined by using sodium fluorescein (NaFlu). Immunohistochemistry for occludin, GFAP and c-fos, western-blot analysis for occludin and electron microscopy for the ultrastructural alterations in BBB were performed. The brain level of NaFlu did not increase in rats with CD and/or kindling. Following administration of a convulsive dose of PTZ, a significant increase in BBB permeability was observed in kindled rats with CD. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Slightly enhanced immunoreactivity for GFAP was observed in all groups except control. c-fos immunoreactivity in brain sections of kindled rats with CD displayed a striking increase by convulsive PTZ challenge. Tight junctions were ultrastructurally intact, whereas markedly increased number of pinocytotic vesicles was noted in brain endothelium of kindled rats with CD by convulsive dose of PTZ. The present study showed that epileptic seizures induced by convulsive PTZ challenge during kindling-mediated epileptogenesis in the presence of CD changed both functional and ultrastructural properties of the BBB and considerably enhanced transendothelial vesicular transport, while paracellular pathway was apparently not involved in this setting. (C) 2008 Elsevier B.V. All Tights reserved.