Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex
Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex
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DOI：
10.1523/jneurosci.1751-04.2004
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发表时间：
2004-09-08
影响因子：
5.3
通讯作者：
Friedman, A
中科院分区：
文献类型：
--
作者：
Seiffert, E;Dreier, JP;Friedman, A
在许多病理条件下，已经报道了人和动物的血脑屏障完整性的扰动。虽然血脑屏障阻止了许多血液成分进入脑细胞外空间，但这种扰动对脑功能的影响及其在皮质疾病发病机制中的作用尚不清楚。大脑皮质在体内暴露于胆盐导致血清白蛋白长期外渗至脑细胞外间隙，并与星形胶质细胞显著活化相关，无炎症反应或显著细胞丢失。使用脑切片的电生理记录，我们发现在治疗后4 - 7天内出现癫痫样放电的病灶，并且在治疗动物的> 60%的脑切片中可以记录到术后49天，但在假手术对照组中很少（10%）。癫痫样活动涉及多巴胺能和GABA能神经传递。直接向皮质应用天然血清、变性血清或含白蛋白的溶液也会诱导癫痫样活动。相比之下，用血清适应的电解质溶液灌注不会诱导异常活动，从而表明无血清脑环境暴露于血清蛋白是血脑屏障破坏的皮质中癫痫发生的基础。虽然许多神经病理学需要一个受损的血脑屏障，这是第一个直接证据表明，它可能有一个局灶性皮质癫痫，一种常见的神经系统疾病的发病机制中的作用。
Perturbations in the integrity of the blood - brain barrier have been reported in both humans and animals under numerous pathological conditions. Although the blood - brain barrier prevents the penetration of many blood constituents into the brain extracellular space, the effect of such perturbations on the brain function and their roles in the pathogenesis of cortical diseases are unknown.In this study we established a model for focal disruption of the blood - brain barrier in the rat cortex by direct application of bile salts. Exposure of the cerebral cortex in vivo to bile salts resulted in long-lasting extravasation of serum albumin to the brain extracellular space and was associated with a prominent activation of astrocytes with no inflammatory response or marked cell loss. Using electrophysiological recordings in brain slices we found that a focus of epileptiform discharges developed within 4 - 7 d after treatment and could be recorded up to 49 d postoperatively in > 60% of slices from treated animals but only rarely (10%) in sham-operated controls. Epileptiform activity involved both glutamatergic and GABAergic neurotransmission. Epileptiform activity was also induced by direct cortical application of native serum, denatured serum, or albumin-containing solution. In contrast, perfusion with serum-adapted electrolyte solution did not induce abnormal activity, thereby suggesting that the exposure of the serum-devoid brain environment to serum proteins underlies epileptogenesis in the blood - brain barrier-disrupted cortex. Although many neuropathologies entail a compromised blood brain barrier, this is the first direct evidence that it may have a role in the pathogenesis of focal cortical epilepsy, a common neurological disease.