Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice.

Academic Article

Abstract

  • 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.
  • Keywords

  • Integrin, Neurogenesis, Neurorepair, Perlecan, Stroke, Animals, Brain, Cells, Cultured, Heparan Sulfate Proteoglycans, Humans, Male, Mice, Mice, Inbred C57BL, Neurogenesis, Neuroprotection, Organ Culture Techniques, Protein Domains, Stroke
  • Digital Object Identifier (doi)

    Author List

  • Trout AL; Kahle MP; Roberts JM; Marcelo A; de Hoog L; Boychuk JA; Grupke SL; Berretta A; Gowing EK; Boychuk CR
  • Start Page

  • 72
  • End Page

  • 86
  • Volume

  • 12
  • Issue

  • 1