Intra-arterial stem cell therapy modulates neuronal calcineurin and confers neuroprotection after ischemic stroke.

Abstract

Aim: 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 injury. The present study investigates the role of IA MSCs in modulating neuronal CaN after stroke onset. Materials and methods: To validate, middle-aged ovariectomized female rats exposed to MCAo (90 min) were treated with IA MSCs (1 × 105 MSCs) or phosphate-buffered saline (PBS) at 6 hours to check CaN expression in different groups.Tests for assessing functional and motor coordination were performed along with biochemical estimations. Furthermore, an inhibition study by non-selective inhibitor of neuronal calcium channel, flunarizine, was performed to explore the possible underlying mechanism by which IA MSCs may interact with CaN. Results: The study suggests that IA MSCs seemingly reduce the expression of CaN after ischemic stroke. IA MSCs have shown to improve the functional outcome and normalize oxidative parameters. Conclusion: Our study provides a preliminary evidence of role of IA MSCs in modulating CaN expression.

• Authors: Jackson Saraf, Deepaneeta Sarmah, Kanchan Vats, Harpreet Kaur, Kanta Pravalika, Madhuri Wanve, Kiran Kalia, Anupom Borah, Kunjan R Dave, Dileep R Yavagal, Pallab Bhattacharya
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 129 Issue 10 Pg. 1039-1044 (Oct 2019) ISSN: 1563-5279 [Electronic] England
• PMID: 31203689 (Publication Type: Journal Article)

Chemical References

• Calcineurin

Topics

• Animals
• Brain Ischemia (metabolism, therapy)
• Calcineurin (biosynthesis)
• Female
• Infusions, Intra-Arterial
• Mesenchymal Stem Cell Transplantation (methods)
• Neurons (metabolism)
• Neuroprotection (physiology)
• Ovariectomy (adverse effects, trends)
• Rats
• Rats, Sprague-Dawley
• Stroke (metabolism, therapy)