Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier J P, Heinemann U, Friedman A
Department of Physiology, Soroka Medical Center and Zlotowski Center for Neuroscience, Ben-Gurion University, Beer-Sheva, Israel.
Neurobiol Dis. 2007 Feb;25(2):367-77. doi: 10.1016/j.nbd.2006.10.006. Epub 2006 Dec 22.
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.
血脑屏障（BBB）的破坏是常见神经系统疾病的一个典型表现。人体数据表明，血脑屏障破坏可能是脑功能障碍的基础。动物实验显示，血脑屏障破坏后会出现癫痫样活动。在本研究中，我们调查了血脑屏障破坏的神经生理学、结构和功能后果。成年大鼠使用脱氧胆酸钠（DOC）在大鼠感觉运动皮层进行局灶性血脑屏障破坏。体内磁共振成像显示早期血脑屏障破坏，随后皮质体积延迟减小。这与神经元数量减少和星形胶质细胞数量增加有关。体外实验表明，治疗1个月后，扩散性抑制的阈值和诱发癫痫电位的传播速度增加。此外，在血脑屏障破坏后的最初几周内，动物的运动功能恶化。血清白蛋白治疗导致了类似的细胞损失，证实了DOC的作用是由于血脑屏障的开放。我们的研究结果表明，在血脑屏障通透的大脑皮层中癫痫病灶形成后，会出现延迟性神经退行性变和功能损害。
