Intra-arterial stem cell therapy modulates neuronal calcineurin and confers neuroprotection after ischemic stroke
Jackson Saraf, Deepaneeta Sarmah, Kanchan Vats, Harpreet Kaur, Kanta Pravalika, Madhuri Wanve, show all
Received 06 Dec 2018, Accepted 11 Jun 2019, Accepted author version posted online: 15 Jun 2019
Download citation https://doi.org/10.1080/00207454.2019.1633315
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Abstract
Calcineurin (CaN) is a threonine/phosphatase which play roles in neuronal homeostasis. Ischemic stroke induces hyperactivation of CaN which further triggers apoptotic signaling. CaN inhibition has limited therapeutic output and neurotoxicity due to its intricate roles in the neuronal network and requires a strategic modulation. Intra-arterial (IA) mesenchymal stem cells (MSCs) have shown to interact with the milieu in a paracrine manner as compared to CaN inhibitors to ameliorate the neuronal damage triggered by ischemia/reperfusion (I/R) injury. The present study investigates the role of IA MSCs in modulating neuronal CaN after stroke onset. To validate,middle-aged ovariectomized female rats exposed to MCAo (90 min) were treated with IA MSCs (1x10^5 MSCs) or phosphate-buffered saline (PBS) at 6 hours to check CaN expression in different groups. Furthermore, an inhibition study by non-selective inhibitor of neuronal calcium channels was performed to explore the possible underlying mechanism by which IA MSCs may interact with CaN.Results suggest that IA MSCs seemingly reduce the expression of CaN after ischemic stroke and have shown improvement in neurodeficit and motor coordination. Our study provides a preliminary evidence of role of IA MSCs in modulating CaN expression and a probable mechanism through which they might interact.
KEY WORDS: Stroke, Stem cell therapy, Calcineurin, Neuroprotection
Jackson Saraf, Deepaneeta Sarmah, Kanchan Vats, Harpreet Kaur, Kanta Pravalika, Madhuri Wanve, show all
Received 06 Dec 2018, Accepted 11 Jun 2019, Accepted author version posted online: 15 Jun 2019
Download citation https://doi.org/10.1080/00207454.2019.1633315
Select Language▼
Translator disclaimer
Accepted author version
Abstract
Calcineurin (CaN) is a threonine/phosphatase which play roles in neuronal homeostasis. Ischemic stroke induces hyperactivation of CaN which further triggers apoptotic signaling. CaN inhibition has limited therapeutic output and neurotoxicity due to its intricate roles in the neuronal network and requires a strategic modulation. Intra-arterial (IA) mesenchymal stem cells (MSCs) have shown to interact with the milieu in a paracrine manner as compared to CaN inhibitors to ameliorate the neuronal damage triggered by ischemia/reperfusion (I/R) injury. The present study investigates the role of IA MSCs in modulating neuronal CaN after stroke onset. To validate,middle-aged ovariectomized female rats exposed to MCAo (90 min) were treated with IA MSCs (1x10^5 MSCs) or phosphate-buffered saline (PBS) at 6 hours to check CaN expression in different groups. Furthermore, an inhibition study by non-selective inhibitor of neuronal calcium channels was performed to explore the possible underlying mechanism by which IA MSCs may interact with CaN.Results suggest that IA MSCs seemingly reduce the expression of CaN after ischemic stroke and have shown improvement in neurodeficit and motor coordination. Our study provides a preliminary evidence of role of IA MSCs in modulating CaN expression and a probable mechanism through which they might interact.
KEY WORDS: Stroke, Stem cell therapy, Calcineurin, Neuroprotection
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