The inflammatory footprints of XXXX -induced oxidative damage in neurovascular components.

@entity167 @entity75 @entity11177 @entity1110 @entity842 @entity6710 @entity1068 @entity3094
Microvessels, the main components of the blood-brain barrier (BBB) are vulnerable to oxidative damage during @entity167 -induced stress. @entity167 produces oxidative damage within the vessels and in the brain. Using our animal model of catheter implant into the common carotid artery (CCA), we trace the footprints of @entity167 -induced oxidative damage and inflammatory process at the BBB and into the brain. The uniqueness of the finding is that @entity1068 causes oxidative damage in all neurovascular components by activating @entity1110 oxidase and inducible @entity842 synthase in the brain. It is not the oxidants but the @entity1068 that traverses through the BBB because we found that the highly reactive @entity6710 does not cross the BBB. Thus, oxidative damage is caused at the site of oxidant production in the microvessels and in the brain. Our data indicate that @entity3094 (the primary metabolite of @entity1068 ) is the inducer/activator of these enzymes that generate oxidants in brain neurovascular cells. Evidence for @entity167 -induced @entity75 is indicated by the alterations of the tight junction protein @entity11177 in intact microvessels. Importantly, we demonstrate that the site of BBB oxidative damage is also the site of immune cells aggregation in the microvessels, which paves the path for inflammatory footprints. These findings reveal the underlying mechanisms that @entity1068 -elicited BBB oxidative damage initiates the brain vascular inflammatory process, which ultimately leads to neuroinflammation.
