Low-intensity focused ultrasound attenuates early traumatic brain injury by OX-A/NF-κB/NLRP3 signaling pathway
Lianghua Huang, Junwei Kang, Gengfa Chen, Wen Ye, Xiangqiang Meng, Qing Du, Zhen Feng
Aging 2022, 14, 7455-7469 · 10.18632/aging.204290
Abstract
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.
Abstract via europepmc.
Exposures
Exposure 1: LIFUS to the hypothalamus after traumatic brain injury
Target: hypothalamus — “hypothalamus region”
Device: Olympus / Panametrics · Olympus · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 0.5 | ✓✓✓⚑ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.518 | ✓✓✓⚑ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Fundamental frequency stated as 500 Hz, on-break ratio 5 %, PRF 250 Hz, total ultrasonic duration 400 ms. Each rat was stimulated for 30 min a day for three consecutive days, starting 20 min after TBI.
Consistency checks: f0 out of range.
Flags from extraction
exposures[0].fundamental_frequency_khz— Text says 'set to 500 Hz' but the same sentence cites a 440 to 700 KHz skull-penetration range, so kHz was probably meant. Recorded as stated (0.5 kHz).exposures[0].timing.pulse_duration_ms— Pulse duration not stated; DC/PRF would give 0.2 ms but it is not computed here.exposures[0].timing— Duty cycle is called an 'on-break ratio'; 400 ms is the 'total ultrasonic duration' of one sonication, repeated for 30 min a day; the nested structure is not fully described.n_subjects— Only group sizes are stated (sham 30, TBI 30, TBI+LIFUS 30, TBI+LIFUS+SB334867 12); only the last two groups received active ultrasound; per-assay n is 6.anaesthesia— TBI induced and drug injected under ether anaesthesia; the anaesthetic state during LIFUS is not stated explicitly.blinding— Only the neurobehavioural testers are stated to be blinded.exposures[0].free_field.ispta_w_cm2— Reported as 518 mW/cm2 in degassed water; recorded as 0.518 W/cm2. Hydrophone-measured through no skull.sham_type— Sham LIFUS: probe placed on head without starting the machine; a separate sham-operation group also exists.