Abstract
Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases, and neural stem cells (NSCs) transplant has been employed for repairing SCI. Ferulic acid (FA) is able to promote neurogenesis in various stem cell therapies. We aimed to investigate the effect of FA on NSC transplant therapy, and the underlying mechanism, in improving functional recovery in SCI rat model. A rat model of SCI was established, which then received transplant of NSCs with or without FA pre-treatment. Functional recovery of the SCI rats was then evaluated, in terms of spinal cord water content, myeloperoxidase activity and behavioral assessments. Effect of FA in inducing hypoxia in NSCs was also assessed, followed by identifying the hypoxic regulated microRNA and the subsequent target gene. Transplant of FA pre-treated NSCs improved functional recovery of SCI rats to a more significant extent than NSCs without FA pre-treatment. The beneficial effects of FA in repairing SCI was mediated by inducing hypoxia in NSCs, which in turn inhibited microRNA-590 to elevate vascular endothelial growth factor expression. Our findings support the clinical potential of FA in improving efficacy of NSC transplant therapy for treatment of SCI.
Highlights
Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases (Wu et al, 2012)
By day 21, BBB score of SCI+Ferulic acid (FA)-neural stem cells (NSCs) rats was significantly higher than SCI+NSC rats, which suggested that FA pre-treatment further enhanced the effect of NSC transplant therapy in reparing SCI
By increasing vascular endothelial growth factor (VEGF) expression, FA is able to improve the efficacy of NSC transplant therapy to repair SCI in a rat model
Summary
Spinal cord injury (SCI) is the leading cause of paralysis, disability and even death in severe cases (Wu et al, 2012). Despite improved medical care, treating SCI patients is still a serious challenge, with slim chance of full functional recovery. Given the unique properties of neuron progenitor cells or neural stem cells (NSCs) in repairing injuries of the nervous system, NSC transplant therapy holds promising potential for SCI patients. Implanting an NSC scaffold into SCI rats could promote long-term recovery of Clinical Potential of FA in Treatment of SCI neurological functions (Teng et al, 2002). In a primate SCI model, transplant of human NSC has exhibited clinical beneficial effects in repairing the injured spinal cords (Iwanami et al, 2005)
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