Abstract
Despite recent advancements in blood vessel recanalization, ischemic stroke remains a leading cause of significant morbidity. Therefore, new stroke therapies are urgently needed, but have thus far failed in clinical trials despite promising animal data. Studies in our lab have suggested that proteolytic fragments of the extracellular matrix heparan sulfate proteoglycan perlecan are neuroprotective and neuroreparative in experimental ischemic stroke. Further studies have suggested that one such fragment, perlecan LG3, is generated by multiple cells of the neurovascular unit in response to the pro-inflammatory cytokine, interleukin-1alpha (IL-1α). Long thought to be deleterious to the brain after stroke, we now provide data that suggests that IL-1α is neuroreparative upon delayed intravenous administration in experimental ischemic stroke. Coupled with other work in our lab that suggests that acute post-stroke IL-1α administration is neuroprotective, we here aim to show that IL-1α is also an attractive therapeutic target in later phases of stroke. 3-month-old C57Bl6 mice underwent transient middle cerebral artery occlusion for one hour and received either vehicle or IL-1α treatment (1ng/mouse) intravenously 3 days following experimental stroke. For up to 14 days after stroke, all groups were evaluated on an 11 point neuroscore. Mice were sacrificed 7 or 14 days post stroke and their brains analyzed for cellular dysmorphia, endothelial cell activation, overall cerebral vascularization, and evidence of neurogenesis at the subventricular zone (SVZ). IL-1α treated mice have less brain dysmorphia (p > 0.0001), greater overall vascularization (p > 0.05), a trending increase in neurogenesis at the SVZ, and significantly improved behavioral outcomes. Collectively, our results suggest that IL-1α could represent an unexpected and novel therapeutic approach for ischemic stroke with a broad therapeutic window.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
