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.
Highlights
Stroke is currently the second leading cause of death worldwide and results in most disability cases [1]
When bone marrow mesenchymal stem cells (BMSC) were incubated with 50 umol/L, 100 umol/L, 200 umol/L, or 300umol/L fasudil, the optical density (OD) values were 0.70, 0.55, 0.44, and 0.53, respectively, exhibiting no difference in the OD value when compared with control (P>0.05)
We demonstrated that 20 umol/L fasudil could facilitate the proliferation of BMSCs and induce their differentiation into neuron-like cells
Summary
Stroke is currently the second leading cause of death worldwide and results in most disability cases [1]. Autologous bone marrow mesenchymal stem cells (BMSCs) exert neuroprotective effects against cerebral ischemia, which may be mediated by autophagy inhibition or an anti-apoptotic mechanism [4, 5]. BMSC transplantation therapy has been proven effective in numerous preclinical experiments, exhibiting neurogenesis, angiogenesis and enhanced neural plasticity in animal cerebral ischemia models [6,7,8]. Several clinical trials have demonstrated the safety and feasibility of BMSC transplantation in patients with ischemic stroke [9]. ROCK inhibitors can reduce the infarct size and improve the functional outcome in patients with focal cerebral ischemia [11]. The current study aimed to investigate the synergistic effects of BMSCs and fasudil in animal models of ischemic stroke
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