Combined Treatment of Bone Marrow Mesenchymal Stem Cells and Fasudil Promotes Neurovascular Remodeling and Neurological Function Recovery in Ischemic Stroke

Appl Biochem Biotechnol. 2022 Feb;194(2):801-812. doi: 10.1007/s12010-021-03679-6. Epub 2021 Sep 20.

Abstract

Stroke remains a highly deadly and disabling disease with limited treatment tragedies due to the limitations of available treatments; novel therapies for stroke are needed. In this article, the synergistic results of dual bone marrow mesenchymal stem cells (BMSC) and fasudil treatment in rat models of ischemic stroke still require further identification. Sprague-Dawley rats were used to construct the middle cerebral artery, occlusion models. BMSCs were incubated with fasudil, and MTT was performed to evaluate cell proliferation. The rats were treated with fasudil + BMSC, BMSC, fasudil, and saline. Blood samples were collected for complete blood count analysis and measurement of serum TNF-α levels. The neurological functions were evaluated. After the rats were sacrificed, immunohistochemical staining and TTC staining was performed. Fasudil promoted the proliferation of BMSCs and induced their differentiation into neuron-like cells. BMSCs increased the proportion of neutrophils; nevertheless, fasudil counteracted the neutrophil increase. The TUJ-1/MAP2/VIII factor expression in the fasudil + BMSC group was significantly higher than that in the other groups. The number of GFAP-positive cells decreased in the fasudil + BMSC and BMSC alone groups. The infarct volume in the fasudil + BMSC and BMSC alone groups was significantly lower than in the fasudil alone and control groups. Both BMSCs and fasudil exert neurorestorative effects in rat models of cerebral ischemia. Fasudil neutralizes the pro-inflammatory effects of BMSCs, while BMSCs and fasudil together had synergistic effects promoting neurovascular remodeling and neurological function recovery in stroke. A combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke.

Keywords: Bone marrow; Fasudil; Infarction; Inflammation; Ischemic stroke; Mesenchymal stem cells; Neurological function.

MeSH terms

  • Stroke*