van Vliet E A, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, Gorter J A
Epilepsy Institute of The Netherlands (SEIN), Heemstede.
Brain. 2007 Feb;130(Pt 2):521-34. doi: 10.1093/brain/awl318. Epub 2006 Nov 22.
Leakage of the blood-brain barrier (BBB) is associated with various neurological disorders, including temporal lobe epilepsy (TLE). However, it is not known whether alterations of the BBB occur during epileptogenesis and whether this can affect progression of epilepsy. We used both human and rat epileptic brain tissue and determined BBB permeability using various tracers and albumin immunocytochemistry. In addition, we studied the possible consequences of BBB opening in the rat for the subsequent progression of TLE. Albumin extravasation in human was prominent after status epilepticus (SE) in astrocytes and neurons, and also in hippocampus of TLE patients. Similarly, albumin and tracers were found in microglia, astrocytes and neurons of the rat. The BBB was permeable in rat limbic brain regions shortly after SE, but also in the latent and chronic epileptic phase. BBB permeability was positively correlated to seizure frequency in chronic epileptic rats. Artificial opening of the BBB by mannitol in the chronic epileptic phase induced a persistent increase in the number of seizures in the majority of rats. These findings indicate that BBB leakage occurs during epileptogenesis and the chronic epileptic phase and suggest that this can contribute to the progression of epilepsy.
血脑屏障（BBB）的渗漏与包括颞叶癫痫（TLE）在内的多种神经系统疾病相关。然而，尚不清楚血脑屏障的改变是否发生在癫痫发生过程中，以及这是否会影响癫痫的进展。我们使用了人类和大鼠的癫痫脑组织，并通过各种示踪剂和白蛋白免疫细胞化学方法测定血脑屏障的通透性。此外，我们研究了大鼠血脑屏障开放对随后颞叶癫痫进展的可能影响。在人类中，癫痫持续状态（SE）后，星形胶质细胞和神经元以及颞叶癫痫患者的海马中白蛋白外渗明显。同样，在大鼠的小胶质细胞、星形胶质细胞和神经元中也发现了白蛋白和示踪剂。癫痫持续状态后不久，大鼠边缘脑区的血脑屏障是通透的，在潜伏期和慢性癫痫期也是如此。慢性癫痫大鼠的血脑屏障通透性与癫痫发作频率呈正相关。在慢性癫痫期用甘露醇人工开放血脑屏障会导致大多数大鼠癫痫发作次数持续增加。这些发现表明，血脑屏障渗漏发生在癫痫发生过程和慢性癫痫期，并提示这可能促进癫痫的进展。
