Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage

Abstract

Purpose: Subarachnoid hemorrhage (SAH) is a common complication of cerebral vascular disease. Hydrogen has been reported to alleviate early brain injury (EBI) through oxidative stress injury, reactive oxygen species (ROS), and autophagy. Autophagy is a programmed cell death mechanism that plays a vital role in neuronal cell death after SAH. However, the precise role of autophagy in hydrogen-mediated neuroprotection following SAH has not been confirmed. Methods: In the present study, the objective was to investigate the neuroprotective effects and potential molecular mechanisms of hydrogen-rich saline in SAH-induced EBI by regulating neural autophagy in the C57BL/6 mice model. Mortality, neurological score, brain water content, ROS, malondialdehyde (MDA), and neuronal death were evaluated. Results: The results show that hydrogen-rich saline treatment markedly increased the survival rate and neurological score, increased neuron survival, downregulated the autophagy protein expression of Beclin-1 and LC3, and endoplasmic reticulum (ER) stress. That indicates that hydrogen-rich saline-mediated inhibition of autophagy and ER stress ameliorate neuronal death after SAH. The neuroprotective capacity of hydrogen-rich saline is partly dependent on the ROS/Nrf2/heme oxygenase-1 (HO-1) signaling pathway. Conclusion: The results of this study demonstrate that hydrogen-rich saline improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and ER stress.

Therapeutic Effects of Hydrogen Gas Inhalation on Trimethyltin-Induced Neurotoxicity and Cognitive Impairment in the C57BL/6 Mice Model

“…Studies have shown that H 2 is highly capable of penetrating the biological membranes including the BBB. Thus, this characteristic of H 2 provides unrestricted access to the CNS, causing therapeutic effects on many CNS diseases, including ischemia stroke, intracranial hemorrhage, and neurodegenerative diseases [41][42][43][44]. Moreover, previous studies have shown that administration of H 2 inhalation attenuated redox stress, inflammatory and OS mediators, and prevented BBB disruption by reducing the activation of mast cells and degranulation that result in amelioration of neurological conditions [24,39,41].…”

Orexin-A exerts neuroprotective effect in experimental intracerebral hemorrhage by suppressing autophagy via OXR1-mediated ERK/mTOR signaling pathway

“…It is a major pathway to remove senescent or damaged organelles and long-lived proteins in eukaryotic cells, and it plays a critical role in maintaining intracellular homeostasis and recycling cellular components. Recently research have been confirmed that autophagy is associated with many CNS disorders, including cerebral ischemia ( Xu et al, 2021 ), trauma ( Cui et al, 2015 ), SAH ( Jiang et al, 2021 ), and ICH ( Yuan et al, 2017 ). In our study, we confirmed that autophagy occurs in the brain after ICH.…”

Evaluation of the effect of enriched hydrogen saline solution on distant organ (lung) damage in skeletal muscle ischemia reperfusion in rats

“…Hydrogen-enriched water has the same antioxidant, anti-inflammatory, and antiapoptotic effects as those of hydrogen inhalation. 35 Indeed, studies have emphasized that HRS has preventive and therapeutic effects in many pathologies, including aplastic anemia, 36 subarachnoid hemorrhages, 37 intestinal damage in hemorrhagic shock, 38 heart dysfunction, 20 cardiopulmonary bypass-induced cerebral damage, 39 renal damage after IR, 40 Alzheimer, 41 burn damage, 42 erythrocyte deformability after limb ischemia, 19 and postoperative cognitive function. 21 Others have demonstrated that HRS may potentially alleviate primary lung IR injury.…”