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

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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.