Effects of hyperbaric oxygen on the Nrf2 signaling pathway in secondary injury following traumatic brain injury

Abstract

ABSTRACT. We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P < 0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P < 0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P < 0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.

TTB Protects Astrocytes Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via Activation of Nrf2/HO-1 Signaling Pathway

“…When Nrf2 is up-regulated and translocated into the nucleus from the cytoplasm under stress conditions, the process is also essential for the activation of HO-1 expression (Kang et al, 2015). Growing evidence demonstrated that the Nrf2/HO-1 signaling pathway participated in the process of oxidative stress in several brain dysfunctional diseases (Meng et al, 2016; Bellaver et al, 2017; Zhao et al, 2018). Several antioxidant ingredients indicated that they protected cell damage by up-regulating Nrf2 and HO-1 expression in various diseases (Hsu et al, 2012; Yao et al, 2015; Jung et al, 2017).…”

Hyperbaric Oxygen Therapy in Traumatic Brain Injury: Cellular and Molecular Mechanisms

“…Based on these results authors assumed that HBOT may diminish the inflammatory response after TBI by inhibiting the activation of inflammasome signaling. Latest results of Meng et al [86] showed that HBOT significantly increased the expression of nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) and heme oxygenase-1, and inhibited the expression of Toll-like receptor 4 and nuclear factor-kappa B in a rat TBI model [87]. Furthermore, HBOT decreases expression of nNOS, eNOS and iNOS (neuronal, endothelial and inducible nitric oxide synthases) mRNA in the cortex after acute traumatic cerebral injury [92].…”

“…Data of many studies has been shown that HBO suppress various mediators of inflammation [54,67,86,87] indicating that the decreased brain edema, blood-brain barrier leakage, cell…”

A review on the neuroprotective effects of hyperbaric oxygen therapy

“… 102 HBOT increased expression of the heme oxygenase, nuclear factor erythroid 2-related factor 2 (Nrf2), and quinine oxidoreductase 1 in the brain tissue around the lesion and also improved neurological function after TBI. 103 A study revealed that HBO reduces IL-1β and IL-18 and suppresses protein expression of inflammasome components, along with high-mobility group box 1 reduction after TBI in the brain and serum. 104 In regard to repetitive mild TBI, it was found that HBOT significantly decreased the magnetic resonance imaging-identified abnormalities and tissue histopathology.…”