Uzüm Gülay, Sarper Diler A, Bahçekapili Nesrin, Ziya Ziylan Y
Istanbul University, Istanbul Medical Faculty Dept. Physiology, 34390, Capa-Istanbul, Turkey.
Life Sci. 2006 Apr 25;78(22):2571-6. doi: 10.1016/j.lfs.2005.10.027. Epub 2005 Dec 15.
Recombinant human erythropoietin (r-Hu EPO) has been shown to exert neuroprotection in ischemic, excitotoxicity, trauma, convulsions and neurodegenerative disorders. Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including neurodegenerative disorders. This study aimed to investigate the effects of r-Hu EPO on BBB integrity in pentylentetrazol (PTZ) induced seizures in rats. Seizures were observed and evaluated regard to latency and intensity for an hour. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage were observed for BBB integrity. r-Hu EPO was given intraperitoneally 24 h prior to seizure induction. Total seizure duration of 720+/-50 s after single PTZ administration (80 mg/kg i.p.) was declined to 190+/-40 s in r-Hu EPO pretreatment. A typical BBB breakdown pattern (i.e. staining in cerebellum, cerebral cortex, midbrain, hippocampus, thalamus and corpus striatum) was observed in rat brains with PTZ induced seizures; whereas, EPO pretreatment confined BBB leakage to cerebellum and cortical areas, and lessened the intensity of tonic-clonic seizures observed in PTZ seizures. The protective effect of r-Hu EPO on BBB permeability in seizures is a new and original finding. The protective action of r-Hu EPO in seizures and some of CNS pathologies warrant further investigations.
重组人促红细胞生成素(r-Hu EPO)已被证明在缺血、兴奋性毒性、创伤、惊厥和神经退行性疾病中具有神经保护作用。血脑屏障(BBB)渗漏在包括神经退行性疾病在内的许多脑部病理状态的发病机制中起作用。本研究旨在探讨r-Hu EPO对戊四氮(PTZ)诱导的大鼠癫痫发作时血脑屏障完整性的影响。观察癫痫发作情况,并在一小时内评估其潜伏期和强度。通过肉眼观察和分光光度法测量伊文思蓝(EB)渗漏情况来评估血脑屏障的完整性。在诱导癫痫发作前24小时腹腔注射r-Hu EPO。单次腹腔注射PTZ(80mg/kg)后总癫痫发作持续时间为720±50秒,而r-Hu EPO预处理后降至190±40秒。在PTZ诱导癫痫发作的大鼠脑中观察到典型的血脑屏障破坏模式(即小脑、大脑皮层、中脑、海马、丘脑和纹状体染色);而EPO预处理将血脑屏障渗漏限制在小脑和皮质区域,并减轻了PTZ癫痫发作中观察到的强直-阵挛性发作的强度。r-Hu EPO对癫痫发作时血脑屏障通透性的保护作用是一项新的原创性发现。r-Hu EPO在癫痫发作和一些中枢神经系统病理状态中的保护作用值得进一步研究。