Studies of vascular biology during the past decade have identified an expanding list of agonists and antagonists that regulate local hemostasis, inflammation, and reactivity in blood vessels. Interactions at the blood-endothelial interface are intricate and complex and have been postulated to play a role in the initiation of stroke and the progression of brain injury during early hours of ischemia, particularly in conjunction with reperfusion injury ( Hallenbeck, 1996 ). In the current study of normal and activated vessels in rat brain, immunoreactive tumor necrosis factor-alpha (TNF-α), heme oxygenase-1 (HO-1), and manganese superoxide dismutase (MnSOD) exhibit concentric perivascular rings involving vessel wall and surrounding parenchyma that appear to coincide with one another in serial sections. The ring patterns 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 all vessels within a high power field (HPF) synchronously. The average number of vessels per HPF (mean ± SD) with perivascular cuffs of immunoreactive MnSOD increased from 51 ± 28 in Wistar, 72 ± 46 in Wistar-Kyoto, and 84 ± 30 in Sprague Dawley rats (no spontaneous strokes) to 184 ± 72 in spontaneously hypertensive stroke-prone rats (spontaneous strokes). Perivascular immunoreactive cuffs are also increased in spontaneously hypertensive rats by induction of cytokine expression by lipopolysaccharide (64 ± 15 vs. 131 ± 32 /HPF). The patterns of TNF-α, HO-1, and MnSOD in naïve animals are interpreted to indicate that focal hemostatic balance normally fluctuates in brain vessels and influences surrounding parenchymal cells. Perivascular immunoreactive cuffs representing this process are more frequent in animals with lipopolysaccharide-induced endothelial activation or genetic stroke proneness.
Brain Vessels Normally Undergo Cyclic Activation and Inactivation: Evidence from Tumor Necrosis Factor-α, Heme Oxygenase-1, and Manganese Superoxide Dismutase Immunostaining of Vessels and Perivascular Brain Cells
