Brain vessels normally undergo cyclic activation and inactivation: Evidence from tumor necrosis factor-alpha, heme oxygenase-1, and manganese superoxide dismutase immunostaining of vessels and perivascular brain cells

Studies of vascular biology during the past decade have identified an expan ding list of agonists and antagonists that regulate local hemostasis, infla mmation, and reactivity in blood vessels. Interactions at the blood-endothe lial interface are intricate and complex and have been postulated to play a role in the initiation of stroke and the progression of brain injury durin g early hours of ischemia, particularly in conjunction with reperfusion inj ury (Hallenbeck, 1996). In the current study of normal and activated vessel s in rat brain, immunoreactive tumor necrosis factor-alpha (TNF-alpha); hem e oxygenase-1 (HO-1), and manganese superoxide dismutase (MnSOD) exhibit co ncentric perivascular rings involving vessel wall and surrounding parenchym a that appear to coincide with one another in serial sections. The ring pat terns suggest periodic radial expansion of these molecules released through a process of cyclic activation and inactivation of brain vessel segments. In this process, the rings appear randomly scattered instead of affecting a ll vessels within a high power field (HPF) synchronously. The average numbe r of vessels per HPF (mean rt SD) with perivascular cuffs of immunoreactive MnSOD increased from 51 +/- 28 in Wistar, 72 +/- 46 in Wistar-Kyoto, and 8 4 +/- 30 in Sprague Dawley rats (no spontaneous strokes) to 184 +/- 72 in s pontaneously hypertensive stroke-prone rats (spontaneous strokes). Perivasc ular immunoreactive cuffs are also increased in spontaneously hypertensive rats by induction of cytokine expression by lipopolysaccharide (64 +/- 15 v s. 131 +/- 32 /HPF). The patterns of TNF-alpha, HO-1, and MnSOD in naive an imals are interpreted to indicate that focal hemostatic balance normally fl uctuates in brain vessels and influences surrounding parenchymal cells. Per ivascular immunoreactive cuffs representing this process are more frequent in animals with polysaccharide-induced endothelial activation or genetic st roke proneness.