Abstract:
Human stroke serum (HSS) has been shown to impair cerebrovascular function, likely by factors released into the circulation after ischemia. 20 nm gold nanoparticles (GNPs) have demonstrated anti-inflammatory properties, with evidence that they decrease pathologic markers of ischemic severity. Whether GNPs affect cerebrovascular function, and potentially protect against the damaging effects of HSS on the cerebral circulation remains unclear. HSS obtained 24 h poststroke was perfused through the lumen of isolated and pressurized third-order posterior cerebral arteries (PCAs) from male Wistar rats with and without GNPs (~2 × 109 GNP/ml), or GNPs in vehicle, in an arteriograph chamber (n = 8/group). All vessels were myogenically reactive ≥60 mmHg intravascular pressure; however, vessels containing GNPs had significantly less myogenic tone. GNPs increased vasoreactivity to small and intermediate conductance calcium activated potassium channel activation via NS309; however, reduced vasoconstriction to nitric oxide synthase inhibition. Hydraulic conductivity and transvascular filtration, were decreased by GNPs, suggesting a protective effect on the blood-brain barrier. The stress-strain curves of PCAs exposed to GNPs were shifted leftward, indicating increased vessel stiffness. This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications.
摘要:
人类中风血清(HSS)已被证明会损害脑血管功能,可能是由于缺血后释放到循环中的因素。20nm的金纳米粒子(GNP)已经证明了抗炎特性,有证据表明它们降低了缺血严重程度的病理标志物。GNP是否影响脑血管功能,并可能防止HSS对脑循环的破坏性影响尚不清楚。卒中后24小时获得的HSS通过有和没有GNP(〜2×109GNP/ml)的雄性Wistar大鼠的孤立且加压的三阶大脑后动脉(PCAs)的管腔进行灌注,或车辆中的GNP,在动脉造影室(n=8/组)。所有血管均为肌源性反应性≥60mmHg血管内压;然而,含有GNP的血管具有明显较少的肌源性张力。GNP通过NS309增加了对小电导和中等电导钙激活钾通道激活的血管反应性;然而,减少血管收缩对一氧化氮合酶的抑制作用。水力传导率和经血管滤过,被GNP减少,对血脑屏障有保护作用.暴露于GNP的PCAs的应力-应变曲线向左移动,表明血管刚度增加。这项研究提供了第一个证据,表明GNP影响脑血管系统的结构和功能,这对它们在生物医学应用中的开发和使用可能很重要。