Stroke-Evoked Angiogenesis Results in a Transient Population of Microvessels

Abstract

The role of angiogenesis after stroke is unclear; if angiogenesis supports long-term recovery of blood flow, then microvessel hyperdensity consequent to angiogenesis should persist in infarcted cortex. Here, we assess the long-term stability of ischemia-induced microvessels after 2-h transient rat middle cerebral artery occlusion (tMCAo) followed by 30, 90, or 165 days of reperfusion. Stereological measures of microvessel density were taken adjacent to and within cortical cysts. Vascular permeability was documented by extravasation of immunoglobulin (IgG) and of fluorescein-dextran. After 30 days reperfusion, a significantly increased microvessel volume density (V V ) was restricted to the inner margin of cystic infarcts as compared with the region external to the infarct or contralateral control cortex (F = 42.675, P < 0.001). The hyperdense ischemic vasculature was abnormally leaky to IgG and fluorescein-dextran. Between 30 and 90 days of reperfusion, this vessel hyperdensity regressed significantly and then regressed further but less drastically between 90 and 165 days. Phagocytic macrophages were restricted to the infarct and dynamic changes in their number correlated with microvessel regression. Additional ED-1 labeled inflammatory cells were widely distributed inside and external to the infarct, even after 165 days of reperfusion. These data show that ischemia evoked angiogenesis results, at least in part, in transient populations of leaky microvessels and phagocytic macrophages. This suggests that a major role of this angiogenesis is for the removal of necrotic brain tissue.

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

“…With regard to the role of angiogenesis after cerebral ischemia, Yu et al [63] proposed that the major function of ischemia-stimulated vessel formation is to eliminate necrotic tissue and debris via macrophages. Wei et al [64] demonstrated that angiogenesis helps to restore blood flow in the ischemic zone by interacting with the arteriole collateral circulation established after cerebral ischemia, thereby improving the long-term recovery of neurological function in rats.…”

Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke

“…Yet, CD14 high CD16 + monocytes could also be beneficial through its richer expression of proangiogenic Tie-2 (Murdoch et al, 2007) and their strong phagocytic activity (Skrzeczynska-Moncznik et al, 2008). Together, angiogenesis and phagocytosis could facilitate the clearance of injured brain tissue after stroke (Manoonkitiwongsa et al, 2001;Yu et al, 2007). The meaning of the high expression of TLR2 in this population remains to be further investigated.…”

“…In experimental ischemia, monocytes can promote inflammation, but they may also contribute to the resolution of inflammation (Manoonkitiwongsa et al, 2001;Yu et al, 2007). In patients with acute stroke, there is a significant increase in the number of circulating monocytes, and this increment is particularly conspicuous in patients who experience a stroke-associated infection (SAI) .…”

A Neurovascular Niche for Neurogenesis after Stroke

“…Stroke opens the BBB in peri-infarct cortex for up to 90 d after infarction (Veltkamp et al, 2005;Yu et al, 2006). To establish BBB permeability in this stroke model, SDF1␤, Ang1, and a function-blocking anti-Tie2 antibody were labeled by fluorescent conjugation and delivered systemically for 5 d after stroke.…”