4.5 Article

Maturation of neural stem cells and integration into hippocampal circuits - a functional study in an in situ model of cerebral ischemia

Journal

JOURNAL OF CELL SCIENCE
Volume 131, Issue 4, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.210989

Keywords

Embryonic neural stem/progenitor cell; Organotypic hippocampal slice; Maturation of neuronal excitability; Stem cell differentiation; Excitatory transmission; Cerebral ischemia

Categories

Funding

  1. State Fund for Fundamental Research of Ukraine [F46.2/001]
  2. National Academy of Sciences of Ukraine (Biotechnology and Functional Genomics grant) [CPV-15/16/17/18]

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The hippocampus is the region of the brain that is most susceptible to ischemic lesion because it contains pyramidalneurons that are highly vulnerable to ischemic cell death. A restricted brain neurogenesis limits the possibility of reversing massive cell death after stroke and, hence, endorses cell-based therapies for neuronal replacement strategies following cerebral ischemia. Neurons differentiated from neural stem/progenitor cells (NSPCs) can mature and integrate into host circuitry, improving recovery after stroke. However, how the host environment regulates the NSPC behavior in post-ischemic tissue remains unknown. Here, we studied functional maturation of NSPCs in control and post-ischemic hippocampal tissue after modelling cerebral ischemia in situ. We traced the maturation of electrophysiological properties and integration of the NSPC-derived neurons into the host circuits, with these cells developing appropriate activity 3 weeks or less after engraftment. In the tissue subjected to ischemia, the NSPC-derived neurons exhibited functional deficits, and differentiation of embryonic NSPCs to glial types - oligodendrocytes and astrocytes was boosted. Our findings of the delayed neuronal maturation in postischemic conditions, while the NSPC differentiation was promoted towards glial cell types, provide new insights that could be applicable to stem cell therapy replacement strategies used after cerebral ischemia.

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