Kopach, O;
Rybachuk, O;
Krotov, V;
Kyryk, V;
Voitenko, N;
Pivneva, T;
(2018)
Maturation of neural stem cells and integration into hippocampal circuits: functional study in post-ischemia in situ.
Journal of Cell Science
, 131
(4)
, Article jcs210989. 10.1242/jcs.210989.
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Abstract
The hippocampus is the most susceptible region of the brain to ischemic lesion, with highly vulnerable pyramidal interneurons to ischemic cell death. A restricted brain neurogenesis limits a withdrawal of massive cell death after stroke that endorses cell-based therapies for neuronal replacement strategies following cerebral ischemia. Neurons differentiated from neural stem/progenitor cells (NSPCs) matured and integrated into host circuitry, improving recovery after stroke. However, how host environment regulates the NSPC behaviour 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 maturation of electrophysiological properties and integration of the NSPC-derived neurons into the host circuits, developing appropriate activity that takes 3 weeks or less after engraftment. In the ischemic-injured tissue, the NSPC-derived neurons exhibited functional deficits and differentiation of embryonic NSPCs was boosted to glial type – oligodendrocytes and astrocytes. Our findings of the delayed neuronal maturation whilst the promoted NSPC differentiation towards glial cell type in post-ischemic conditions provide new insights into stem-cell-therapy for replacement strategies in cerebral ischemia.
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