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J Cell Sci. 2018 Feb 20;131(4). pii: jcs210989. doi: 10.1242/jcs.210989.

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

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Department of Sensory Signalling, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine
Institute of Neurology, University College London, London WC1N 3BG, UK.
Department of Sensory Signalling, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
State Institute of Genetic and Regenerative Medicine, Kyiv 04114, Ukraine.
Kyiv Academic University, Kyiv 03142, Ukraine.


The hippocampus is the region of the brain that is most susceptible to ischemic lesion because it contains pyramidal neurons 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 post-ischemic 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.


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

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