Cytokine induced changes observed in cerebral vascular reactivity in cerebral microcirculation using intaraviatal microscopy : a new model of periventricular leukomalacia

TNF-α水平的升高与新生儿脑室周围白质软化的风险增加呈递进关系。本研究旨在探讨正常大鼠腹腔注射TNF-α对脑小动脉内血管活性物质的反应性变化。采用颅窗法，通过活体显微镜观察脑小动脉。测定正常大鼠脑血管对去甲肾上腺素（NE） （0.01 ~ 10 μg/kg/min）和血管紧张素II (AT II) （0.01 ~ 10 μg/kg/min）的反应性。此外，我们评估了腹腔注射TNF-α (25μg/kg)诱导的AT-II （1μg/kg/min）脑血管反应性的变化。给药0.01、0.1、1、10 μg/kg/min可诱导剂量依赖性小动脉血管收缩。当NE浓度为10 μg/kg/min时，最大血管收缩率为29±14%。另一方面，0.01、0.1、1、10 μg/kg/min ATⅱ均未引起大鼠动脉血管明显收缩。腹腔注射TNF-α后，观察到脑血管对APⅱ的反应性发生显著变化。TNF-α组血管收缩率由对照组的7±5%提高至23±14% （p<0.05）。我们的数据表明，脑动脉对AT-II的反应不同于对NE的反应，TNF-α调节脑动脉对AT-II的反应。

A progressive relationship was noted between increasing TNF-α levels and increased risk of neonatal periventricular leukomalacia. The purpose of this study was to determine the changes in cerebral vascular reactivity to vasoactive substances in the cerebral arteriole of normal rats indeuced by intraperitoneal administration of TNF-α.Cerebral arterioles were observed by intravital microscopy assisted by a video imager with cranial window method. We determined the cerebral vascular reactivity to norepinephrine (NE) (0.01〜10 μg/kg/min) and angiotensin II (AT II) (0.01〜10 μg/kg/min) in normal rats. Furthermore, we evaluated the changes in cerebral vascular reactivity to AT-II (1μg/kg/min) indeced by intraperitoneal administration of TNF-α (25μg/kg).The administration of 0.01, 0.1, 1, 10 μg/kg/min NE induced dose-dependent arteriolar vasoconstriction. Maximum vasoconstriction of 29±14% was attained at a concentration of 10 μg/kg/min NE. On the other hand, the administration of 0.01, 0.1, 1, 10 μg/kg/min AT II did not induced significant arteriolar vasoconstriction. A significant change in cerebral vascular reactivity to AP II was observed after intraperitoneal administration of TNF-α. Vasoconstriction of 7±5% in control group was increased to 23±14% in TNF-α administered group (p<0.05).Our data suggest that cerebral arterial response to AT II is different from the response to NE, and TNF-α modulates cerebral arterial response to AT-II.