Mechanisms of Mitochondrial Oxidative Stress in Brain Injury: From Pathophysiology to Therapeutics

Abstract

Mitochondrial oxidative stress has been implicated in various forms of brain injury, both traumatic and non-traumatic. Due to its oxidative demand, the brain is intimately dependent on its mitochondrial functioning. However, there remains appreciable heterogeneity in the development of these injuries regarding ROS and their effect on the sequelae. These include traumatic insults such as TBIs and intracranial hemorrhaging secondary to this. In a different vein, such injuries may be attributed to other etiologies such as infection, neoplasm, or spontaneous hemorrhage (strokes, aneurysms). Clinically, the manner of treatment may also be adjusted in relation to each injury and its unique progression in the context of ROS. In the current review, then, the authors highlight the role of mitochondrial ROS in various forms of brain injury, emphasizing both the collective and unique elements of each form. Lastly, these narratives are met with the current therapeutic landscape and the role of emerging therapies in treating reactive oxygen species in brain injuries.

Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species

“…Oxidative stress occurs due to an imbalance between the generation and detoxification of free radicals, increasing reactive species [ 34 ]. This equilibrium is disrupted in several acute brain injuries, including TBI and stroke [ 121 , 171 , 172 ], and chronic neurodegenerative diseases [ 173 ]. For instance, studies have demonstrated that SOD activity decreases 24 h following a TBI and continues to be reduced 7 days after a severe TBI [ 121 ].…”