Hydrogen inhalation protects hypoxic–ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats

Abstract:

Hypoxic–ischemic brain damage (HIBD) is one of the leading causes of brain injury in infant with high risk of mortality and disability; therefore, it is important to explore more feasible and effective treatment strategies. Here, we assessed the neuroprotective effects of different hydrogen inhalation times for the treatment of HIBD. We induced hypoxia–ischemia in Sprague–Dawley rats (postnatal day 7, both sexes), followed by treatment with hydrogen inhalation for 30, 60, or 90 min. Morphological brain injury was assessed by Nissl and TUNEL staining. Acute inflammation was evaluated by examining the expression of interleukin-1β (IL-1β) and NF-κB p65, as well as Iba-1 immunofluorescence in the brain. Neural apoptosis was evaluated by examining the expression of P-JNK and p53 as well as NeuN immunofluorescence. Neurobehavioral function of rats was evaluated by Morris water maze test at 36 days after surgery. The results showed that hypoxia–ischemia injury induced the inflammatory response of microglia; however, these changes were inhibited by hydrogen inhalation. The inhibitory effects became more apparent as the treatment duration increased (P < 0.05). Furthermore, hypoxia–ischemia induced neuronal damage and increased the expression of the apoptotic factors, P-JNK, and p53, which were attenuated by hydrogen inhalation (P < 0.05). Hypoxia–ischemia caused long-term spatial memory deficits during brain maturation, which were ameliorated by hydrogen inhalation (P < 0.01). In conclusion, hypoxia–ischemia induced severe long-term damage to the brain, which could be alleviated by hydrogen inhalation in a time-dependent manner.