Traumatic brain injury: Mechanisms, manifestations, and visual sequelae

Abstract

Traumatic brain injury (TBI) results when external physical forces impact the head with sufficient intensity to cause damage to the brain. TBI can be mild, moderate, or severe and may have long-term consequences including visual difficulties, cognitive deficits, headache, pain, sleep disturbances, and post-traumatic epilepsy. Disruption of the normal functioning of the brain leads to a cascade of effects with molecular and anatomical changes, persistent neuronal hyperexcitation, neuroinflammation, and neuronal loss. Destructive processes that occur at the cellular and molecular level lead to inflammation, oxidative stress, calcium dysregulation, and apoptosis. Vascular damage, ischemia and loss of blood brain barrier integrity contribute to destruction of brain tissue. This review focuses on the cellular damage incited during TBI and the frequently life-altering lasting effects of this destruction on vision, cognition, balance, and sleep. The wide range of visual complaints associated with TBI are addressed and repair processes where there is potential for intervention and neuronal preservation are highlighted.

Keywords: contrast sensitivity; headache; light sensitivity; neuroinflammation; oxidative stress; traumatic brain injury; visual acuity.

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.

FIGURE 2

Pupillary reflexes. The diameter of the pupil changes in response to specific conditions such as variations in object distance and level of illumination. The accommodation reflex, an adjustment for near vision, results in pupillary constriction, and inward rotation of the eyes as an object draws nearer. Dim lighting elicits pupillary dilation as does emotional arousal. Increased brightness of lighting causes pupillary constriction and the effect is both direct (affecting the eye exposed to the light) and consensual with constriction of the pupil in the eye opposite to the light-stimulated eye.