Hydrogen improves cell viability partly through inhibition of autophagy and activation of PI3K/Akt/GSK3β signal pathway in a microvascular endothelial cell model of traumatic brain injury

ABSTRACT

Objective：Traumatic brain injury (TBI) is one of the most serious public health problems in the world. Hydrogen (H₂), a flammable, colorless, and odorless gas, has been observed to have preventive and therapeutic effects on brain trauma and other neurological disorders, but its exact mechanism has not been fully clarified.

Methods: To further study the mechanism underlying the role of hydrogen gas in alleviating BBB damage after TBI, we performed the scratch injury model on cultured brain microvascular endothelial cells (bEnd.3), which formed the microvascular endothelial barrier – an integral part of the highly specialized BBB.

Results: In the case of TBI, hydrogen was able to improve the decline of cell viability induced by TBI. More importantly, inhibition of PI3 K/Akt/GSK3β signal pathway or activation of autophagy reduced the protective effect of hydrogen on cell viability, indicating that such protective effect was regulated by PI3 K/Akt/GSK3β signal pathway and was related to the inhibition of autophagy.

Conclusion: So we concluded that hydrogen improved the cell viability in a microvascular endothelial cell model of TBI partly through inhibition of autophagy, and inhibitory effect of hydrogen on autophagy was exerted by activating PI3 K/Akt/GSK3β signal pathway. These findings enriched our knowledge about the mechanism of hydrogen therapy against TBI.

KEYWORDS:

• Hydrogen
• blood-brain barrier
• brain microvascular endothelial barrier
• traumatic brain injury
• autophagy

Acknowledgments

The authors thank all individuals for participating in the study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Natural Science Foundation of Tianjin Municipal Science and Technology Commission; under Grant Nos. 18JCQNJC81100; and the Youth Incubation Foundation of General Hospital of Tianjin Medical University; under Grant Nos. ZYYFY2017036.

Notes on contributors

Yifeng Wang

Yifeng Wang is a medical doctor in the Department of Geriatrics and Intensive care at Tianjin Medical University General Hospital. His research focuses on the mechanism of hydrogen therapy for traumatic brain injury.

Lu Wang

Lu Wang is a medical doctor in the Department of Geriatrics at Tianjin Medical University General Hospital. Her research focuses on the mechanism of hydrogen therapy for traumatic brain injury.

Tianpeng Hu

Tianpeng Hu is a doctoral student in the Department of Geriatrics at Tianjin Medical University General Hospital. His research focuses on the mechanism of hydrogen therapy for traumatic brain injury.

Feng Wang

Feng Wang is a medical doctor in the Department of Geriatrics at Tianjin Medical University General Hospital. His research focuses on the mechanism of cognitive function in rats with high-fat diet consumption.

Zhaoli Han

Zhaoli Han is a medical doctor in the Department of Geriatrics at Tianjin Medical University General Hospital. His research focuses on exploring novel therapeutic strategies for traumatic brain injury and chronic traumatic encephalopathy based on microglia derived exosomes.

Zhenyu Yin

Zhenyu Yin is a doctoral student in the Department of Geriatrics at Tianjin Medical University General Hospital. His research focuses on exploring novel therapeutic strategies for traumatic brain injury and chronic traumatic encephalopathy based on microglia derived exosomes.

Xintong Ge

Xintong Ge is a medical doctor in the Department of Neurosurgery at Tianjin Medical University General Hospital. His research focuses on exploring novel therapeutic strategies for traumatic brain injury and chronic traumatic encephalopathy based on microglia derived exosomes and pyroptosis regulation.

Keliang Xie

Keliang Xie is a medical doctor in the Department of Anesthesiology at Tianjin Medical University General Hospital. His research focuses on the mechanism of hydrogen therapy for Sepsis.

Ping Lei

Ping Lei is a medical doctor in the Department of Geriatrics at Tianjin Medical University General Hospital. His research focuses on exploring novel therapeutic strategies for traumatic brain injury and chronic traumatic encephalopathy.