Seawater Immersion Aggravates Early Mitochondrial Dysfunction and Increases Neuronal Apoptosis After Traumatic Brain Injury.

ABSTRACT

Traumatic brain injury (TBI) is a major cause of death and disability in naval warfare. Due to the unique physiochemical properties of seawater, immersion in it exacerbates TBI and induces severe neural damage and complications. However, the characteristics and underlying mechanisms of seawater-immersed TBI remain unclear. Mitochondrial dysfunction is a major cause of TBI-associated brain damage because it leads to oxidative stress, decrease in energy production, and apoptosis. Thus, the present study aimed to further elucidate the current understanding of the pathology of seawater-immersed TBI, particularly the role of mitochondrial dysfunction, using a well-defined rat model of fluid percussion injury and a stretch injury model comprising cultured neurons. The biochemical and pathological markers of brain-related and neuronal injuries were evaluated. Histological analysis suggested that seawater immersion enhanced brain tissue injury and induced a significant increase in apoptosis in rats with TBI. Additionally, lactate dehydrogenase release occurred earlier and at higher levels in stretched neurons at 24 h after seawater immersion, which was consistent with more severe morphological changes and enhanced apoptosis. Furthermore, seawater immersion induced more rapid decreases in mitochondrial membrane potential, adenosine triphosphate (ATP) content, and H+-ATPase activity in the cortices of TBI rats. In addition, the immunochemical results revealed that seawater immersion further attenuated mitochondrial function in neurons exposed to stretch injury. The increases in neuronal damage and apoptosis triggered by seawater immersion were positively correlated with mitochondrial dysfunction in both in vivo and in vitro models. Thus, the present findings strengthen the current understanding of seawater-immersed TBI. Moreover, because seawater immersion aggravates mitochondrial dysfunction and contributes to post-traumatic neuronal cell death, it is important to consider mitochondria as a therapeutic target for seawater-immersed TBI.