Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis

Background: Traumatic brain injury (TBI)-induced acute lung injury (ALI) is a critical condition, and inflammation and apoptosis play essential roles. Molecular hydrogen (H-2) exerts anti-inflammatory and anti-apoptotic effects. Our previous work has shown that 42% H-2 can improve TBI. In the current study, we tested the hypothesis that inhalation of hydrogen (42% H-2, 21% O-2, balanced nitrogen) for 1 h per day can improve TBI-induced ALI. Methods: Sprague-Dawley male rats were randomly divided into 3 groups. Except for the sham group (group S), rats were subjected to a fluid percussion injury (FPI) and the H-2 treatment group were given inhaled hydrogen for 1 h per day. We evaluated the lung function, pyroptosis and apoptosis at 24 h, 48 h and 72 h. Results: Compared with group S, the rats in the TBI group (group T) showed obvious pulmonary edema after a TBI. Inhalation of high-concentration hydrogen significantly improved the rats. During this process, rats had some tendency to heal on their own, and H-2 also accelerated the self-healing process. Lung injury scores, oxygenation index and pulmonary edema were consistent. Compared with group S, the pyroptosis-related proteins Caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and Gasdermin-D (GSDM-D) in the lung tissues of the rats in group T were significantly increased after a TBI. In the H-2 treatment group (group H), these proteins were significantly decreased. The levels of IL-1 beta and IL-18 were significantly increased after TBI while in group H were significantly decreased. At the same time, cleaved caspase-3 and BCL-2/Bax were also changed after H-2 treatment. These demonstrates the powerful ameliorating effect of H-2 on pyroptosis, apoptosis and systemic inflammation. However, rats also had tendency to heal on their own, and H-2 also accelerated the self-healing process at the same time. Conclusions: H-2 improves TBI-ALI, and the mechanism may be due to the decrease of both pyroptosis and apoptosis and the alleviation of inflammation. These findings provide a reference and evidence for the use of H-2 in TBI-ALI patients in the intensive care unit (ICU).