The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis is an important component of chronic post-stroke repair, and previous studies have implicated perlecan in developmental neurogenesis, we hypothesized that domain V could have a broad therapeutic window by enhancing neurogenesis after stroke. We demonstrated that domain V is chronically increased in the brains of human stroke patients, suggesting that it is present during post-stroke neurogenic periods. Furthermore, perlecan deficient mice had significantly less neuroblast precursor cells after experimental stroke. Seven-day delayed domain V administration enhanced neurogenesis and restored peri-infarct excitatory synaptic drive to neocortical layer 2/3 pyramidal neurons after experimental stroke. Domain V’s effects were inhibited by blockade of α2β1 integrin, suggesting the importance of α2β1 integrin to neurogenesis and domain V neurogenic effects. Our results demonstrate that perlecan plays a previously unrecognized role in post-stroke neurogenesis and that delayed DV administration after experimental stroke enhances neurogenesis and improves recovery in an α2β1 integrin-mediated fashion. We conclude that domain V is a clinically relevant neuroprotective and neuroreparative novel stroke therapy with a broad therapeutic window.
|Number of pages||15|
|Journal||Translational Stroke Research|
|State||Published - Feb 2021|
Bibliographical noteFunding Information:
This work was funded by the National Institutes of Health R21 NS079960 (GB), the National Institutes of Health R21 NS088608 (BS), the National Institutes of Health R01 NS092552 (BS), the American Heart Associtation (MK), the Sir Charles Hercus Fellowship from the Health Research Council of New Zealand, a Health Research Council of New Zealand project grant and the Royal Society of New Zealand Marsden Fund (AC), and the Neurological Foundation of New Zealand project grant (AB & AC). Acknowledgments
© 2020, The Author(s).
ASJC Scopus subject areas
- Neuroscience (all)
- Clinical Neurology
- Cardiology and Cardiovascular Medicine