Nature Communications (Oct 2024)

Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke

  • Suvra Nath,
  • Jose C. Martínez Santamaría,
  • Yu-Hsuan Chu,
  • James S. Choi,
  • Pasquale Conforti,
  • Jia-Di Lin,
  • Roman Sankowski,
  • Lukas Amann,
  • Christos Galanis,
  • Kexin Wu,
  • Sachin S. Deshpande,
  • Andreas Vlachos,
  • Marco Prinz,
  • Jae K. Lee,
  • Christian Schachtrup

DOI
https://doi.org/10.1038/s41467-024-53217-1
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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Abstract After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia–NSPC ligand–receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke.