OBJECTIVE
Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of
vascular endothelial growth factor (
VEGF) in cultured endothelial cells. The
VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce
neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of
VEGF in damaged neural tissue and improved locomotor function after
spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of
VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the
neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the
therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and
thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for
VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and
5-HT was performed on spinal cord sections taken 42 days after SCI.
Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and
thermal allodynia following SCI. In the double staining, expression of
VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by
Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes
VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the
neuroprotective effect of
VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.