Research Paper Volume 14, Issue 18 pp 7455—7469
Low-intensity focused ultrasound attenuates early traumatic brain injury by OX-A/NF-κB/NLRP3 signaling pathway
- 1 Department of Rehabilitation Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
Received: May 20, 2022 Accepted: August 3, 2022 Published: September 16, 2022https://doi.org/10.18632/aging.204290
How to Cite
Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Traumatic brain injury (TBI) is a serious hazard to human health and is characterized by high rates of disability and mortality. It is necessary to explore new effective treatment methods to reduce the impact of TBI on individuals and society. As an emerging neuromodulation technique, ultrasound is used to treat some neurological diseases, but the neuroprotective mechanism of low-intensity focused ultrasound (LIFUS) in TBI remains unclear. We aimed to investigate the protective effects and potential mechanisms of LIFUS in TBI.
Methods: A rat model of TBI was established using the free-fall method. After establishing the TBI model, the hypothalamus region was covered with LIFUS radiation, and an orexin receptor 1 (OXR1) antagonist (SB334867) was injected intraperitoneally. Neurobehavioral examination, Nissl staining, hematoxylin and eosin staining of the brain tissue, and brain water content, were performed 3 days later. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence staining, and immunohistochemical staining, were used to evaluate the neuroprotective mechanisms of LIFUS.
Results: LIFUS improved tissue damage, neurological deficits, and brain edema. LIFUS can increase the expression of orexin-A (OX-A) and OXR1, significantly inhibit the activation of nuclear factor-κB (NF-κB) protein and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome after TBI, and reduce the release of pro-inflammatory factors after TBI; however, SB334867 can reverse this effect.
Conclusions: This study suggests that LIFUS may play a neuroprotective role by promoting the release of OX-A from the hypothalamus and inhibiting the inflammatory response after TBI through the OX-A /NF-κB/NLRP3 pathway.
ASC: apoptosis-associated speck-like protein; 5-HT: 5-hydroxytryptamine; BDNF: brain-derived neurotrophic factor; CRS-R: Coma Recovery Scale-Revised scores; DA: dopamine; DMSO: dimethyl sulfoxide; DBS: deep brain stimulation; GABA: gamma-aminobutyric acid; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; GDNF: glial cell line-derived neurotrophic factor; H&E: Hematoxylin and Eosin; IL: interleukin; LIFUS: low-intensity focused ultrasound; mNSS: Modified Neurological Severity Scale; MRI: magnetic resonance imaging; NF-κB: nuclear factor-κB; NLRP3: nucleotide-binding domain-like receptor protein 3; OX-A: orexin-A; OXR1: orexin receptor 1; PBS: phosphate-buffered saline; PRF: pulse repetition frequency; qRT-PCR: quantitative real-time polymerase chain reaction; SD: standard deviation; TBI: traumatic brain injury; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor; VNS: vagus nerve stimulation.