Angiogenesis after stroke is correlated with increased numbers of macrophages: The clean-up hypothesis

Brain cells manufacture and secrete angiogenic peptides after focal cerebra l ischemia, but the purpose of this angiogenic response is unknown. Because the maximum possible regional cerebral blood flow is determined by the qua ntity of microvessels in each unit volume, it is possible that angiogenic p eptides are secreted to generate new collateral channels; other possibiliti es include neuroprotection, recovery/regeneration, and removal of necrotic debris. If the brain attempts to create new collaterals, microvessel densit y should increase significantly after ischemia. Conversely, if angiogenic-s ignaling molecules serve some other purpose, microvessel densities may incr ease slightly or not at all. To clarify, the authors measured microvessel d ensities with quantitative morphometry. Left middle cerebral arteries of ad ult male Sprague-Dawley rats were occluded with intraluminal nylon suture f or 4 hours followed by 7, 14, 19, or 30 days of reperfusion. Controls recei ved no surgery or suture occlusion. Changes in microvessel density and macr ophage numbers were measured by light microscopic morphometry using semiaut omated stereologic methods. Microvessel density increased only in the ische mic margin adjacent to areas of pannecrosis and was always associated with increased numbers of macrophages. Ischemic brain areas without macrophages displayed no vascularity changes compared with normal animals. These data s uggest that ischemia-induced microvessels are formed to facilitate macropha ge infiltration and removal of necrotic brain.