Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex
Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex
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DOI：
10.1016/j.nbd.2006.10.006
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发表时间：
2007-02-01
影响因子：
6.1
通讯作者：
Friedman, A.
中科院分区：
文献类型：
--
作者：
Tomkins, O.;Friedman, O.;Friedman, A.
血脑屏障（BBB）的破坏是常见神经系统疾病的特征性发现。人类数据表明，血脑屏障破坏可能是脑功能障碍的基础。动物实验表明，在血脑屏障破坏后癫痫样活动的发展。在本研究中，我们调查了BBB中断的神经生理，结构和功能的后果。成年大鼠进行局灶性血脑屏障破坏大鼠感觉运动皮质使用胆盐脱氧胆酸钠（DOC）。体内磁共振成像显示早期血脑屏障破坏，皮质体积延迟减少。这与神经元数量减少和星形胶质细胞数量增加有关。离体实验表明，治疗后1个月，癫痫诱发电位的传播速度和扩散性抑制阈值增加。此外，在BBB破坏后的最初几周内，动物的运动功能恶化。用血清白蛋白处理导致类似的细胞损失，证实DOC的作用是由于BBB的开放。我们的研究结果表明，迟发性神经退行性变和功能障碍发生后的发展，在BBB渗透性大脑皮层的癫痫灶。(c)2006年爱思唯尔公司All rights reserved.
Disruption of the blood-brain barrier (BBB) is a characteristic finding in common neurological disorders. Human data suggest BBB disruption may underlie cerebral dysfunction. Animal experiments show the development of epileptiform activity following BBB breakdown. In the present study we investigated the neurophysiological, structural and functional consequences of BBB disruption. Adult rats underwent focal BBB disruption in the rat sensory-motor cortex using the bile salt sodium deoxycholate (DOC). Magnetic resonance imaging in-vivo showed an early BBB disruption with delayed reduction in cortical volume. This was associated with a reduced number of neurons and an increased number of astrocytes. In-vitro experiments showed that the threshold for spreading depression and the propagation velocity of the evoked epileptic potentials were increased 1 month after treatment. Furthermore, animals' motor functions deteriorated during the first few weeks following BBB disruption. Treatment with serum albumin resulted in a similar cell loss confirming that the effect of DOC was due to opening of the BBB. Our findings suggest that delayed neurodegeneration and functional impairment occur following the development of the epileptic focus in the BBB-permeable cerebral cortex. (c) 2006 Elsevier Inc. All rights reserved.