Abstract 164: IL-1a Enhances Angiogenic Neurorepair After Experimental Ischemic Stroke
Stroke is a major cause of death and disability worldwide. Unfortunately, all clinical trials that have targeted the primary cerebral ischemia (CI) injury mechanisms of oxidative stress and excitotoxicity have failed. However, CI also induces a potent local inflammatory response that leads to damage in the ischemic penumbra but may also, less acutely, initiate and sustain post-stroke repair processes such as angiogenesis. We hypothesize that the pro-inflammatory cytokine IL-1α promotes angiogenesis after stroke via generation of pro-angiogenic perlecan laminin globular domain 3 (LG3) protein fragments from the brain extracellular matrix. This is based on our previous observations that LG3 is rapidly and persistently generated after CI in vivo, and that IL-1α causes cells of the neurovascular unit to generate LG3 in vitro. Importantly, the potential role of IL-1α in brain angiogenesis has not been previously studied. We now report that IL-1α activates primary brain endothelial cells (BECs) in vitro and significantly enhances several stages of BEC angiogenesis including proliferation and capillary tube-like structure morphogenesis. Furthermore, after experimental stroke (distal transient middle cerebral artery occlusion) in adult C57Bl6 mice, IL-1α levels are chronically (21 days) elevated (measured by qPCR and ELISA) suggesting that IL-1α is persists beyond the acute stroke phase to affect post-stroke angiogenic repair. Finally, IL-1α deficient mice have diminished post-stroke penumbral angiogenesis. Our results collectively suggest that inflammatory mediators such as IL-1α, in addition to their acute deleterious effects, may play an important and previously unrecognized role in post-stroke neurorepair that could be therapeutically exploited.
Author Disclosures: K. Guell: None. E. Pinteaux: None. G. Bix: None.
- © 2015 by American Heart Association, Inc.