Bone marrow-derived mesenchymal stem cell and simvastatin treatment leads to improved functional recovery and modified c-Fos expression levels in the brain following ischemic stroke

Document Type: Original Article

Authors

1 Neuroscience Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Electrophysiology Research Centre, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran,

4 Departmentof Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Department of Anatomy, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

6 Genetics and Development Division, Krembil Research Institute, Toronto, ON, Canada

Abstract

Objective(s): The beneficial outcomes of bone marrow-derived mesenchymal stem cell (BMSC) treatment on functional recovery following stroke has been well established. Furthermore, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have also been shown to increase neuronal survival and promote the movement of BMSCs towards the sites of inflammation. However, the precise mechanisms mediating the improved neurological functional recovery in stoke models following a combination treatment of Simvastatin and BMSCs still remained poorly understood.
Materials and Methods: Here, an embolic stroke model was used to experimentally induce a focal ischemic brain injury by inserting a preformed clot into the middle cerebral artery (MCA). Following stroke, animals were treated either with an intraperitoneal injection of Simvastatin, an intravenous injection of 3 ×106 BMSCs, or a combination of these two treatments.
Results: Seven days after ischemia, the combination of Simvastatin and BMSCs led to a significant increase in BMSC relocation, endogenous neurogenesis, arteriogenesis and astrocyte activation while also reducing neuronal damage when compared to BMSC treatment alone (PConclusion: These results further demonstrate the synergistic benefits of a combination treatment and help to improve our understanding of the underlying mechanisms mediating this beneficial effect.

Keywords

Main Subjects


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