Molecular hydrogen inhalation attenuates postoperative cognitive impairment in rats

Abstract

Postoperative cognitive decline is a major clinical problem with high morbidity and mortality after surgery. Many studies have found that molecular hydrogen (H2) has significant neuroprotection against acute and chronic neurological injury by regulating inflammation and apoptosis. In this study, we hypothesized that H2 treatment could ameliorate the development of cognitive impairment following surgery. Adult male rats were subjected to stabilized tibial fracture operation under anesthesia. Two percent of H2 was inhaled for 3 h beginning at 1 h after surgery. Separate cohorts of rats were tested for cognitive function with fear conditioning and the Y-maze test, or euthanized to assess blood-brain barrier integrity, and systemic and hippocampal proinflammatory cytokine and caspase-3 activity. Surgery-challenged animals showed significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after operation, which were significantly improved by H2 treatment. Furthermore, H2 treatment significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, H2 treatment markedly improved blood-brain barrier integrity and reduced caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that H2 treatment could significantly mitigate surgery-induced cognitive impairment by regulating inflammation and apoptosis.

Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model

“…In our previous report, maternal H 2 administration reduced both the excessive microglial activation and the increased IL-6 levels in the MIA fetal brains 12 , which could ameliorate the behavioral deficits later in life. Previous studies in adult rodents reported that H 2 treatment could mitigate the behavioral dysfunctions, including short-term memory deficits, cognitive impairments, and depressive-like behaviors, by regulating inflammation and ROS production 67 , 68 , which is in line with our current results. Moreover, the present study demonstrated that prenatal H 2 administration restored the MIA-induced neuronal and oligodendrocytic loss, and suppressed the excessive activation of astrocytes at postnatal 5 weeks.…”

Molecular hydrogen: a preventive and therapeutic medical gas for various diseases

“…Recent findings suggest that H 2 treatment is neuroprotective in patients with cerebral I/R injury [ 54 ]. H 2 also mitigates surgery-induced cognitive impairment [ 55 ], decreases lung graft injury [ 56 ] and radiation-induced skin injury in rats [ 57 ], and attenuates lipopolysaccharide-induced acute lung injury in mice [ 14 ].…”

Hydrogen Inhalation Attenuates Oxidative Stress Related Endothelial Cells Injury After Subarachnoid Hemorrhage in Rats

“…Previous studies have shown that hydrogen therapy could improve neurological outcome in animal models of ischemic and hemorrhagic cerebral stroke (Zhan et al, 2012;Zhuang et al, 2012;Shao et al, 2016;Wang et al, 2016;Ono et al, 2017). Hydrogen inhalation can attenuate postoperative cognitive impairment by regulating inflammation and apoptosis in a rat model (Xin et al, 2017). However, long-term outcomes following hydrogen inhalation after SAH has not been previously studied.…”

“…Hydrogen (H 2 ) was administered to experimental rats by inhalation, which was started 0.5 h after the induction of SAH. Hydrogen administration was performed following procedures described in a previous study (Xin et al, 2017). Thus, rats were placed in a transparent chamber that had an inlet connected with 3.3% hydrogen gas inhaler (MIZ, MHG-2000, Japan).…”