Edrissi Hamidreza, Schock Sarah C, Cadonic Robert, Hakim Antoine M, Thompson Charlie S
Universiy of Ottawa, Neuroscience Graduate Program, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5.
Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5.
Brain Res. 2016 Sep 1;1646:494-503. doi: 10.1016/j.brainres.2016.06.036. Epub 2016 Jun 24.
Cerebral small vessel disease (CSVD) is a pathological process leading to lacunar infarcts, leukoaraiosis and cerebral microbleeds. Dysfunction of the blood brain barrier (BBB) has been proposed as a mechanism in the progression cerebral small vessel disease. A rodent model commonly used to study some aspects of CSVD is bilateral common carotid artery occlusion (BCCAO) in the rat. In the present study it was determined that gait impairment, as determined by a tapered beam test, and BBB permeability increased following BCCAO. Cilostazol, a type III phosphodiesterase inhibitor, has been shown to have anti-apoptotic effects and prevent white matter vacuolation and rarefaction induced by BCCAO in rats. In this study the protective effect of cilostazol administration on the increase BBB permeability following BCCAO was determined as well as the effect on plasma levels of circulating microparticles (MPs), cerebral white matter rarefaction, glial activation and gait disturbance. The effect of cilostazol on in vitro endothelial barriers was also evaluated. Cilostazol treatment improved BBB permeability and reduced gait disturbance, visual impairment and microglial activation in optic tract following BCCAO in vivo. It also reduced the degree of cell death and the reduction in trans-endothelial electrical resistance (TEER) in artificial endothelial barriers in vitro induced by MP treatment of in vitro barriers.
脑小血管病(CSVD)是一种导致腔隙性梗死、脑白质疏松和脑微出血的病理过程。血脑屏障(BBB)功能障碍被认为是脑小血管病进展的一种机制。一种常用于研究CSVD某些方面的啮齿动物模型是大鼠双侧颈总动脉闭塞(BCCAO)。在本研究中,通过锥形梁试验确定,BCCAO后步态障碍以及BBB通透性增加。西洛他唑是一种III型磷酸二酯酶抑制剂,已被证明具有抗凋亡作用,并可预防BCCAO诱导的大鼠白质空泡化和稀疏化。在本研究中,确定了西洛他唑给药对BCCAO后BBB通透性增加的保护作用以及对循环微粒(MPs)血浆水平、脑白质稀疏化、胶质细胞活化和步态障碍的影响。还评估了西洛他唑对体外内皮屏障的作用。西洛他唑治疗改善了体内BCCAO后BBB的通透性,并减少了步态障碍、视力损害和视束中的小胶质细胞活化。它还降低了体外人工内皮屏障中MP处理诱导的细胞死亡程度和跨内皮电阻(TEER)的降低。