Grafted neural progenitor cells persist in the injured site and differentiate neuronally in a rodent model of cardiac arrest-induced global brain ischemia.

Meyer, Patricia; Grandgirard, Denis; Lehner, Marika; Haenggi, Matthias; Leib, Stephen (2020). Grafted neural progenitor cells persist in the injured site and differentiate neuronally in a rodent model of cardiac arrest-induced global brain ischemia. Stem cells and development, 29(9), pp. 574-585. Mary Ann Liebert 10.1089/scd.2019.0190

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Hypoxic-ischemic brain injury is the leading cause of disability and death after successful resuscitation from cardiac arrest, and, to date, no specific treatment option is available to prevent subsequent neurofunctional impairments. The hippocampal cornu ammonis segment 1 (CA1) is one of the brain areas most affected by hypoxia, and its degeneration is correlated with memory deficits in patients and corresponding animal models. The aim of the present work was to evaluate the feasibility of neural progenitor cell (NPC) transplantation into the hippocampus in a refined rodent cardiac arrest model. Adult rats were subjected to 12 minutes of potassium-induced cardiac arrest and followed up to 6 weeks. Histological analysis showed extensive neuronal cell death specifically in the hippocampal CA1 segment, without any spontaneous regeneration. Neurofunctional assessment revealed transient memory deficits in ischemic animals compared to controls, detectable after 4, but not after 6 weeks. Using stereotactic surgery, embryonic NPCs were transplanted in a subset of animals 1 week after cardiac arrest and their survival, migration and differentiation were assessed histologically. Transplanted cells showed a higher persistence in the CA1 segment of animals after ischemia. Glia in the damaged CA1 segment expressed the chemotactic factor SDF-1, while transplanted NPCs expressed its receptor CXCR4, suggesting that the SDF-1/CXCR4 pathway, known to be involved in the migration of neural stem cells towards injured brain regions, directs the observed retention of cells in the damaged area. Using immunostaining, we could demonstrate that transplanted cells differentiated into mature neurons. In conclusion, our data document the survival, persistence in the injured area and neuronal differentiation of transplanted NPCs, and thus their potential to support brain regeneration after hypoxic-ischemic injury. This may represent an option worth further investigation in order to improve the outcome of patients after cardiac arrest.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Meyer, Patricia; Grandgirard, Denis; Lehner, Marika; Hänggi, Matthias and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1547-3287

Publisher:

Mary Ann Liebert

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

07 Feb 2020 14:26

Last Modified:

03 May 2020 01:35

Publisher DOI:

10.1089/scd.2019.0190

PubMed ID:

31964231

BORIS DOI:

10.7892/boris.139497

URI:

https://boris.unibe.ch/id/eprint/139497

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