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Hyperbaric oxygen alleviates the activation of NLRP?3?inflammasomes in traumatic brain injury.

ABSTRACT: Growing evidence has demonstrated that the nucleotide?binding oligomerization domain?like receptor family pyrin domain containing 3 (NLRP?3) inflammasome?mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP?3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on interleukin (IL)?1? and IL?18 expression were assessed, as well as NLRP?3 inflammasome activation following TBI. HBO may improve motor score and reduce brain edema, accompanied with the reduction of IL?1? and IL?18 during the 7?day observation period. Furthermore, HBO suppressed mRNA and protein expression of NLRP?3?inflammasome components, especially reducing NLRP?3 expression in microglia. Thus, these results suggested that HBO alleviates the inflammatory response in experimental TBI via modulating microglial NLRP?3?inflammasome signaling.

SUBMITTER: Qian H

PROVIDER: S-EPMC5646971 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Hyperbaric oxygen alleviates the activation of NLRP‑3‑inflammasomes in traumatic brain injury.

Qian Huihui H Li Qinghe Q Shi Woda W

Molecular medicine reports 20170724 4

Growing evidence has demonstrated that the nucleotide‑binding oligomerization domain‑like receptor family pyrin domain containing 3 (NLRP‑3) inflammasome‑mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP‑3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on i ...[more]

PMID: 29067455

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Project description:Persistent postconcussion syndrome (PPCS) after mild traumatic brain injury (mTBI) is a significant public health and military problem for which there is limited treatment evidence. The aim of this study was to determine whether forty 150 kPa hyperbaric oxygen therapies (HBOTs) can improve symptoms and cognitive function in subjects with the PPCS of mTBI, using a randomized controlled crossover design with 2-month follow-up. Sixty-three civilian and military subjects with mTBI/PPCS were randomized to either 40 HBOTs at 150 kPa/60 minutes, once daily, 5 days per week in 8 weeks or an equivalent no-treatment control period. The Control Group was then crossed over to HBOT. Subjects underwent symptom, neuropsychological, and psychological testing, before and after treatment or control with retesting 2 months after the 40th HBOT. Fifty subjects completed the protocol with primary outcome testing. HBOT subjects experienced significant improvements in Neurobehavioral Symptom Inventory, Memory Index, Automated Neuropsychological Assessment Metrics, Hamilton Depression Scale, Hamilton Anxiety Scale, Post-Traumatic Stress Disorder Checklist, Pittsburgh Sleep Quality Index, and Quality Of Life after Brain Injury compared to the Control Group. After crossing over to HBOT the Control Group experienced near-identical significant improvements. Further improvements were experienced by both groups during the 2-month follow-up period. These data indicate that 40 HBOTs at 150 kPa/60 minutes demonstrated statistically significant improvements in postconcussion and Post-Traumatic Stress Disorder symptoms, memory, cognitive functions, depression, anxiety, sleep, and quality of life in civilian and military subjects with mTBI/PPCS compared to controls. Improvements persisted at least 2 months after the 40th HBOT. The study was registered on ClinicalTrials.gov (NCT02089594) on March 18, 2014 and with the U.S. Food and Drug Administration under Investigational New Drug #113823. The Institutional Review Boards of the United States Army Medical Research and Materiel Command Office of Research Protections Human Research Protection Office and the Louisiana State University School of Medicine (approval No. 7381) approved the study on May 13, 2014 and December 20, 2013, respectively.

Project description:Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epidemic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military subjects aged 18-65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam, neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle ear barotrauma (n = 6), transient deterioration in symptoms (n = 7), reversible bronchospasm (n = 1), and increased anxiety (n = 2; not related to confinement); unrelated to HBOT: ureterolithiasis (n = 1), chest pain (n = 2). Significant improvement (29 subjects) was seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexterity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects' SPECT was significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in 75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced a significant reduction in suicidal ideation and reduction in psychoactive medication use.

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Hyperbaric oxygen alleviates the activation of NLRP?3?inflammasomes in traumatic brain injury.

Publications

Hyperbaric oxygen alleviates the activation of NLRP‑3‑inflammasomes in traumatic brain injury.

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