Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat- and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury

Abstract

The clinical application of hyperbaric oxygen therapy (HBOT) in spinal cord injury (SCI) has been reported, however the mechanism underlying its therapeutic effects remains to be elucidated. In the present study, SCI was modeled in male Sprague‑Dawley rats. A total of 120 rats were randomly divided into four groups: Sham‑operated group (SH); sham‑operated and hyperbaric oxygen group (SH+HBO); spinal cord injury group (SCI) and spinal cord injury and hyperbaric oxygen treatment group (SCI+HBO). The rats in each group were randomly divided into five smaller groups (12 h, 1, 3, 7 and 14 days after surgery). The mRNA and protein expression levels of NACHT domain‑, leucine‑rich‑repeat‑ and pyrin domain‑containing protein 3 (NALP3) inflammasome, including NALP3, adaptor molecule apoptosis‑associated speck‑like protein (ASC) and caspase‑1 were determined at several time points following injury. The results of the present study demonstrated that HBOT compromised the mRNA and protein expression levels of NALP3, ASC and caspase‑1 in the SCI model rats and HBOT mitigated SCI‑induced interleukin 1β release in the injured spinal cord tissue. It was concluded that HBOT is an effective approach, which can prevent against spinal cord injury, likely by inactivating NALP3 inflammasome.

Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model

“…In consequence, the administration of anti-ASC neutralizing antibodies to injured rats resulted in significant tissue sparing and functional improvement [6]. Most recently, it has been found that the expression levels of NALP, ASC, and caspase-1 are increased after SCI in rats and that hyperbaric oxygen treatment mitigated this effect [7].…”

Inflammasome: Its role in traumatic brain and spinal cord injury

“…Further, we found that NLRP3 activation occurs in different neural cell types including microglia, astroglia, and neurons (Zendedel et al, ). Similarly, high levels of NLRP3 expression was described in a SCI model (Liang et al, ). Taken together, it seems quite evident that SCI causes an activation of different types of inflammasomes in different cell types.…”

Hyperbaric oxygen therapy of spinal cord injury

“…Many recent studies have investigated the effect of HBO on the inflammatory processes that follow SCI 2024252631323435. In 2010, a rat model involving clip compression injury of the spinal cord at T 8–9 showed decreased inflammatory cytokines, IL-1β and TNF-α, and decreased myeloperoxidase (MPO), an indicator of neutrophil infiltration, after a single HBO treatment immediately after SCI; additionally, increased level of the anti-inflammatory cytokine IL-10 was observed in the HBO therapy group, indicating that HBO not only reduces inflammatory mediators, but also promotes an anti-inflammatory phenotype 20…”

“…The NALP3 inflammasome is a multimeric protein complex consisting of NALP3, ASC, and caspase-1, that mediates IL-1β production and release, which in turn induces further inflammatory cytokine release 65. Daily HBO therapy significantly decreased mRNA and protein expression of NALP3 at 1, 3, and 7 days post-SCI, whereas mRNA and protein levels of ASC and caspase-1 were significantly decreased at 3 and 7 days post-SCI; furthermore, IL-1β levels were also significantly reduced at 3 and 7 days post-SCI 35. Given that reactive oxygen species can trigger NALP3 inflammasome signaling in retinal pigment epithelial cells, Liang et al3566 proposed that the decreased expression of NALP3, ASC, caspase-1, and IL-1β after HBO therapy resulted from the previously evidenced ability of HBO therapy to decrease ROS generation.…”