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

Traumatic brain injury (TBI)-induced acute lung injury (ALI) is a critical condition, and inflammation and apoptosis play essential roles. Molecular hydrogen (H2) exerts anti-inflammatory and anti-apoptotic effects. Our previous work has shown that 42% H2 can improve TBI. In the current study, we tested the hypothesis that inhalation of hydrogen (42% H2, 21% O2, balanced nitrogen) for 1 h per day can improve TBI-induced ALI.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 H2 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.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 H2 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 H2 treatment group (group H), these proteins were significantly decreased. The levels of IL-1β 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 H2 treatment. These demonstrates the powerful ameliorating effect of H2 on pyroptosis, apoptosis and systemic inflammation. However, rats also had tendency to heal on their own, and H2 also accelerated the self-healing process at the same time.H2 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 H2 in TBI-ALI patients in the intensive care unit (ICU).