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Article

Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats

1
Department of Neurology, University of Eastern Finland, FI-70210 Kuopio, Finland
2
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI-70150 Kuopio, Finland
3
Faculty of Medicine and Health Technology, Tampere University, P.O. Box 607, FI-33014 Tampere, Finland
4
Research, Development and Innovation Centre, Tampere University Hospital, P.O. Box 2000, FI-33521 Tampere, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Anuska Andjelkovic
Int. J. Mol. Sci. 2021, 22(4), 1512; https://doi.org/10.3390/ijms22041512
Received: 19 January 2021 / Accepted: 29 January 2021 / Published: 3 February 2021
(This article belongs to the Section Molecular Neurobiology)
Microglia are involved in the post-stroke immunomodulation of brain plasticity, repair, and reorganization. Here, we evaluated whether adipose-tissue-derived mesenchymal stem cells (ADMSCs) and/or rehabilitation improve behavioral recovery by modulating long-term perilesional inflammation and creating a recovery-permissive environment in a rat model of ischemic stroke. Methods: A two-way mixed lymphocyte reaction was used to assess the immunomodulatory capacity of ADMSCs in vitro. Two or 7 days after permanent middle cerebral artery occlusion (pMCAO), rats were intravenously administered ADMSCs or vehicle and housed in a standard or enriched environment (EE). Behavioral performance was assessed with a cylinder test, then we performed stereological and ImageJ/Fiji quantifications of ionized calcium-binding adaptor molecule 1 (Iba1) cells and blood–brain barrier (BBB) leakage. Results: Human ADMSCs were immunosuppressive in vitro. The cylinder test showed partial spontaneous behavioral recovery of pMCAO rats, which was further improved by combined ADMSCs and housing in EE on days 21 and 42 (p < 0.05). We detected an ischemia-induced increase in numbers, staining intensity, and branch length of Iba1+ microglia/macrophages as well as BBB leakage in the perilesional cortex. However, these were not different among pMCAO groups. Conclusion: Combined cell therapy and rehabilitation additively improved behavioral outcome despite long-term perilesional microglia presence in stroke rats. View Full-Text
Keywords: stroke; microglia; inflammation; blood–brain barrier; repair; reorganization; cell therapy; rehabilitation; spontaneous recovery stroke; microglia; inflammation; blood–brain barrier; repair; reorganization; cell therapy; rehabilitation; spontaneous recovery
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MDPI and ACS Style

Bakreen, A.; Juntunen, M.; Dunlop, Y.; Ugidos, I.F.; Malm, T.; Miettinen, S.; Jolkkonen, J. Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats. Int. J. Mol. Sci. 2021, 22, 1512. https://doi.org/10.3390/ijms22041512

AMA Style

Bakreen A, Juntunen M, Dunlop Y, Ugidos IF, Malm T, Miettinen S, Jolkkonen J. Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats. International Journal of Molecular Sciences. 2021; 22(4):1512. https://doi.org/10.3390/ijms22041512

Chicago/Turabian Style

Bakreen, Abdulhameed, Miia Juntunen, Yannick Dunlop, Irene F. Ugidos, Tarja Malm, Susanna Miettinen, and Jukka Jolkkonen. 2021. "Additive Behavioral Improvement after Combined Cell Therapy and Rehabilitation Despite Long-Term Microglia Presence in Stroke Rats" International Journal of Molecular Sciences 22, no. 4: 1512. https://doi.org/10.3390/ijms22041512

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