Mitochondrial specific therapeutic targets following brain injury

Abstract

Traumatic brain injury is a complicated disease to treat due to the complex multi-factorial secondary injury cascade that is initiated following the initial impact. This secondary injury cascade causes nonmechanical tissue damage, which is where therapeutic interventions may be efficacious for intervention. One therapeutic target that has shown much promise following brain injury are mitochondria. Mitochondria are complex organelles found within the cell. At a superficial level, mitochondria are known to produce the energy substrate used within the cell called ATP. However, their importance to overall cellular homeostasis is even larger than their production of ATP. These organelles are necessary for calcium cycling, ROS production and play a role in the initiation of cell death pathways. When mitochondria become dysfunctional, they can become dysregulated leading to a loss of cellular homeostasis and eventual cell death. Within this review there will be a deep discussion into mitochondrial bioenergetics followed by a brief discussion into traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. The review will conclude with a discussion pertaining to the therapeutic approaches currently being studied to ameliorate mitochondrial dysfunction following brain injury. This article is part of a Special Issue entitled SI:Brain injury and recovery.

Keywords: Electron transport chain; Mitochondria; Mitochondrial dysfunction; TBI; Therapeutics; Traumatic brain injury.