Mark N. Rubin, MD

Greenberg DA. Poststroke Angiogenesis, Pro: Making the Desert Bloom. Stroke. 2015

Adamczak J, and Hoehn M. Poststroke angiogenesis, Con: The Dark Side of Angiogenesis. Stroke. 2015

This installment of the “Controversy” series involves what to make of post-stroke angiogenesis: the hypoxia-triggered generation of new capillaries after a stroke of any subtype. The fact that angiogenesis exists in the post-stroke setting–experimental and clinical–is not the point of debate but to what degree this process influences patient outcome. Experimental, pathological case study and treatment trial data exist in this field, but a fundamental clinical question remains unanswered: does manipulating this pathophysiologic process make patients better?

Dr. Greenberg from the Buck Institute for Research on Aging proposes that post-stroke angiogenesis is a viable therapeutic target, mostly because it is fairly well understood at a biochemical level, broadly applicable across the patient population and there are myriad promising biochemical targets in the process that have not yet been investigated. Furthermore, there is the optimistic view that angiogenesis allows for more rapid clearing of ischemic debris, setting a clean slate for post-stroke neuronal reorganization (e.g., functional recovery). Prof. Doctors Adamczak and Hoehn from the Max Planck Institute argue that angiogenesis is more demolition crew than architect. While not arguing that restoration of cerebral blood flow is beneficial to neuronal tissue, they point out the double-edged sword of pro-angiogenic factors (namely Vascular Endothelial Growth Factor, better known as VEGF), which also promote increased cerebral edema which is injurious to brain. They cite evidence that supporting anti-angiogenic factors actually decreases infarct volume.

Dr. Liu from UCSF ties the debate together with a resounding “you’re probably both right but we don’t know enough in general. Plus, how does this all relate to collateralization, which is so hot right now?” She also suggests a careful marriage of nanotechnology and pharmacotherapy may help deliver the right mix of biochemicals–whichever those may be–to the right place at the right time, thus mitigating the known inefficacy and/or risks of systemic delivery of pro-angiogenic factors.

Read on for details of the Basic Science Controversy In Stroke!