Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury

Abstract

Object Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether lowenergy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. Methods Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. Results In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01). Conclusions The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function

“…Some studies show that ESWT can increase the expression of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells cultured in vitro 1,2. At the same time, in the disease model of chronic myocardial ischemia, myocardial infarct, and peripheral vascular disease, low-energy ESWT can increase the expression of VEGF and VEGF receptor, fms-like tyrosine kinase 1 (Flt-1), in vivo and promote vascular regeneration and functional recovery 1–3. Therefore, VEGF integrated with Flt-1 and together, they play the role of reconstructing the tissue after vascular injury in chronic myocardial ischemia, myocardial infarct, and peripheral vascular disease.…”

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

“…The BBB scale has been widely used to evaluate the functional recovery of rats after SCI. 23 In the overexpressed miR-124 and si- PDXK groups, a few necrotic neurons in the spinal cord gray matter, the complete axonal structure in the white matter axonal and the clear lamellar structure in the myelin were observed. These results confirmed that miR-124 overexpression or PDXK gene silencing improved the ability of BMSCs to repair injured spinal cord tissues.…”

Extracorporeal Shock Wave Therapy Decreased Spasticity in Stroke

“…Exploratory activity and nerve regeneration were evaluated using an immunohistochemical experiment. The study results indicated an increase of sensory and functional recovery of muscles and regeneration of damaged nerves in the behavioral and immunohistochemical evaluation after ESWT [7] [8].…”