FIGURE 1.

Cascade of cellular events driven by traumatic brain injury (TBI). TBI incites a series of responses that include excitotoxicity, mitochondrial damage, oxidative stress, neuroinflammation, and cell death. Key mediators in each pathological event is identified. Excess glutamate causes overactivation of N-Methyl-d-aspartate receptors (NMDAr) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAr) which induces neuronal overexcitation and swelling. Mitochondrial damage follows as a result of excess influx of intracellular calcium and uncoupling of the electron transport chain. The precipitous rise of reactive oxygen species and the brain parenchyma’s relatively low antioxidant capacity promotes oxidative stress. Neuroinflammation induces secondary damage via the release of proinflammatory cytokines, chemokines, and inflammatory mediators and ultimately leads to cell death.