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大鼠单次及反复戊四氮诱导癫痫发作后血脑屏障通透性及脑组织微量元素浓度的变化

Changes in the blood-brain barrier permeability and in the brain tissue trace element concentrations after single and repeated pentylenetetrazole-induced seizures in rats.

作者信息

Sahin D, Ilbay G, Ates N

机构信息

Department of Physiology, Faculty of Medicine, Kocaeli University, Derince 41900 Kocaeli, Turkey.

出版信息

Pharmacol Res. 2003 Jul;48(1):69-73.

Abstract

The behaviour of brain capillary endothelium to the passage of macromolecules in single and repeated seizures conditions and its relationship to the brain trace element concentrations are the main subject of this study. For this purpose, animals were treated with either single or repeated doses of pentylenetetrazole (PTZ). As a marker of blood-brain barrier (B-BB) permeability changes, Evans Blue (EB) dye was used. Seizure activity was observed and seizure patterns and convulsion times were recorded. PTZ treatment induced generalised tonic-clonic seizure in all animals, but seizures were found to be lasting longer in single seizure group than repeated seizures group. Seizures induced by single dose PTZ treatment resulted in bilateral EB leakage in the preoptic area, caudate nucleus, putamen, thalamus, hypothalamus, midbrain, and the superior colliculus. However, repeated PTZ-induced seizures led to EB leakage in the brains of only few number of rats, and it was confined to hypothalamus, caudate nucleus, cerebellum, thalamus, and pons. On the other hand, while the levels of copper (Cu) and iron (Fe) in brain tissue were found to be decreased significantly in the repeated seizures group when compared with the other groups, the levels of zinc (Zn) did not show any differences between groups. These results indicate that the regional B-BB opening markedly differs between single and repeated PTZ-induced seizures group and this difference may be due to PTZ tolerance and changes in cerebral endothelial structure.

摘要

在单次和反复癫痫发作条件下脑毛细血管内皮对大分子物质通过的行为及其与脑微量元素浓度的关系是本研究的主要课题。为此,用单次或重复剂量的戊四氮(PTZ)对动物进行处理。作为血脑屏障(B-BB)通透性变化的标志物,使用伊文思蓝(EB)染料。观察癫痫发作活动并记录癫痫发作模式和惊厥时间。PTZ处理在所有动物中诱发全身性强直阵挛性发作,但发现单次发作组的发作持续时间比反复发作组更长。单次剂量PTZ处理诱发的癫痫发作导致视前区、尾状核、壳核、丘脑、下丘脑、中脑和上丘出现双侧EB渗漏。然而,反复PTZ诱发的癫痫发作仅导致少数大鼠脑内出现EB渗漏,且局限于下丘脑、尾状核、小脑、丘脑和脑桥。另一方面,与其他组相比,反复癫痫发作组脑组织中的铜(Cu)和铁(Fe)水平显著降低,而锌(Zn)水平在各组之间未显示出任何差异。这些结果表明,单次和反复PTZ诱发的癫痫发作组之间区域B-BB的开放情况明显不同,这种差异可能是由于PTZ耐受性和脑内皮结构的变化所致。

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