Pathophysiological pathways in mild traumatic brain injury

Mild traumatic brain injury (mTBI) is a disorder of physiologic dysfunction of the brain from trauma, and is the most common form of traumatic brain injury across all age groups.^1,2,3,6 Its clinical manifestations are diverse, ranging from loss of consciousness, dizziness, seizures, headache, irritability, lethargy which are immediately recognized, but a small subset of patients are left with prolonged somatic and cognitive symptoms affecting their quality of life and academic functioning.^4,9,10 Insight into the pathophysiology of mTBI has shown that it is a complex process where mechanical force to the neuron triggers a cascade of multiple reactions at the cellular and molecular level, starting with disruption of ionic homeostasis, glutamate-mediated excitotoxicity, mitochondrial dysfunction, altered cerebral blood flow, neuroinflammation, glial activation, and traumatic axonal injury.^{5,13-19,21-24} There is a mismatch between energy supply and demand of the brain, which further potentiates the injury.^16,30 Although the standard consideration is that mTBI is not accompanied by structural changes, insight into pathophysiological mechanisms reveals that structural changes, some of which are permanent are also seen in mild TBI. This review summarizes the key pathophysiological alterations and processes in mTBI and briefly discusses biomarkers and advanced imaging techniques that may support clinical detection, especially in patients with protracted and prolonged symptoms.