Abstract
Spinal cord injury (SCI) is associated with limited functional recovery. Despite advances in neuroscience, realistic therapeutic treatments for SCI remain unavailable. In this study, the effects of non-invasive ultrasound (US) treatment on behavior and inflammatory responses were evaluated in a rat model of SCI. Adult female Sprague–Dawley rats were subjected to spinal cord contusion injury. Two different US parameters (SCIU5: 5% and SCIU40: 40% duty cycle) were applied, and their effects on behavioral recovery after SCI were quantified. Tissue and neuronal responses were detected. Immunofluorescence was used to detect inflammatory markers. In the rat model of SCI, motor function was more effectively restored, and the lesion cavity area was smaller in the SCIU5 group. Furthermore, the SCIU5 protocol elicited an anti-inflammatory response at the injury site by reducing degenerative FJC-labeled neurons, macrophage/microglia activation, and infiltration. Thus, the lesion area decreased, and tissue density increased. Meanwhile, the SCIU40 protocol did not improve motor function or induce an anti-inflammatory response at the injury site. The SCIU5 protocol effectively accelerated the rate of improved exercise performance in the rat model while reducing inflammation. Accordingly, appropriate US stimulation may represent a promising treatment modality for SCI with beneficial anti-inflammatory effects.
Highlights
Spinal cord injury (SCI) is associated with limited functional recovery
The SCIU5 and SCIU40-treated group had a significantly lower number of degenerating neuronal cells compared to that in the sham control (Fig. 2g–i). These results suggest that SCIU40 treatment tends to increase nerve damage and that SCIU5 treatment has an inhibitory effect on tissue and nerve damage in acute SCI
Preclinical studies have reported that US application results in functional recovery and has neuroprotective effects in neurodegenerative and traumatic diseases via modulation of inflammation and neuroregeneration processes[35,36]
Summary
Spinal cord injury (SCI) is associated with limited functional recovery. Despite advances in neuroscience, realistic therapeutic treatments for SCI remain unavailable. The effects of non-invasive ultrasound (US) treatment on behavior and inflammatory responses were evaluated in a rat model of SCI. The SCIU40 protocol did not improve motor function or induce an anti-inflammatory response at the injury site. Preclinical studies have reported transcranial US stimulation results in functional recovery and neuroprotective effects in neurodegenerative diseases via induction of brain-derived neurotrophic factor (BDNF)[35,36]. These results raise the possibility that US stimulation could block inflammatory reactions and neuronal damage while promoting neuronal regeneration. We demonstrated that US stimulation improves locomotor behavior, reduces tissue/neuronal damage, and inflammatory responses by infiltrating immune cells. The observed anti-inflammatory effects support the potential clinical application of US to develop efficient and safe SCI treatments
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