Microvascular and arterial remodeling induced by chronic hypoperfusion

Abstract

Atherosclerotic stenosis may induce chronic hypoperfusion of the brain when it is severe. Extremely high degree of stenosis which could cause cerebral hypoperfusion was reported to have a paradoxically lower risk of stroke development and less severe stroke when it develops. In the previous study, vascular remodeling and ischemic tolerance induced by chronic hypoperfusion were suggested as the probable mechanisms. However, it remains uncertain which type of vascular remodeling process, that is arteriogenesis or angiogenesis, occurs and from when it is observed after induction of cerebral hypoperfusion if it presents. This study was aimed to document temporal course of vascular remodeling and molecular expression related to arteriogenesis and angiogenesis after induction of sublethal cerebral hypoperfusion. Cerebral hypoperfusion was induced in wistar rats with the bilateral common carotid artery (CCA) ligation. Regional cerebral perfusion (rCP) was measured in the territory of the middle cerebral artery by laser Doppler flowmetry (LDF). Latex angiography was performed. Protein expression was examined by the western blot. The rCP was decreased by 40.2% immediately after bilateral CCA ligation, when compared with the baseline, and recovered to the baseline level 14 days later. Increased arterial diameter, arterial tortuosity, and increased vascular density were observed at 1 week after bilateral CCA ligation. Connexin 37 was also increased at 1 week and decreased to the baseline level at 3 weeks, after bilateral CCA ligation. The levels of vascular endothelial growth factor and fibroblast growth factor-2 were not changed. In the vascular remodeling induced by sublethal cerebral hypoperfusion, arteriogenesis appeared to play a key role and to start within 1 week.