Investigating the Role of VGF and Its Associated Neuropeptides in Post-Stroke Recovery and Repair

Abstract

The high incidence of stroke worldwide as well as the poor efficacy of neuroprotective drugs has shifted the focus of research towards therapies targeting stroke recovery and rehabilitation. VGF (non-acronym), a secreted protein that is processed into several neuropeptides, has been identified as a post-stroke repair molecule playing a role in neurogenesis and the modulation of neuroinflammation. In the present study, we assess the requirement for VGF and its specific peptides during post‐stroke neurogenesis and behavioural recovery. Using a photothrombotic stroke model we induced stroke in the left frontal cortex of wild type and VGF cKO mice. Following stroke, behavioral tests were performed to measure sensorimotor deficits over a four-week period. Finally, mice were sacrificed and used to assess the levels of neurogenesis and neuroinflammation at timepoints ranging from 1‐28 days post‐stroke. We have used gain‐ and loss‐of‐function experiments to demonstrate that VGF and its derived peptides can improve recovery following photothrombotic stroke in the sensorimotor cortex. Preliminary results indicate that VGF peptides increase mobilization of NSCs from the ventricular zone. Further investigation is required to define the precise mechanism underlying the functional recovery and to fully determine the effectiveness of VGF as a relevant therapeutic for post‐stroke recovery in the future.