Table 10: Pathophysiology of concussion and traumatic brain injury [27, 28].

(1) Excessive or indiscriminate release of excitatory neurotransmitters
 Increased glutamate binding to NMDA receptors causes efflux of potassium out of the cell, influx of calcium, and alteration of the neuronal membrane potential: Na-K pump is upregulated and consequently requires more ATP.
(2) An uncoupling of glucose metabolism and cerebral blood flow occurs
 A glucose hypermetabolism ensues and there is a simultaneous diminished cerebral blood flow, which may be reduced as much as 50% of normal
 Even more important from a clinical point of view, the cerebral glucose may be reduced for up to 4 weeks
 (measured by PET brain scan in humans)
(3) Calcium accumulation occurs
 Intracellular Ca++ accumulation causes mitochondrial impairment, cell death by phosphokinases, protein kinases, NO synthase, endonucleases, and calpains and plasmalogenase culminating in free radical accumulation and apoptosis.
(4) Chronic alterations in neurotransmission
 Glutaminergic, cholinergic, and adrenergic alterations account for the memory and cognitive deficits seen after concussion and  TBI. The neurochemical findings include LTP may be persistently impaired after TBI, loss of cholinergic input from the basal forebrain, and impaired GABA inhibitory function of the hippocampal dentate granule cells occurs which predisposes the injured brain to seizures.
(5) Axonal disconnection occurs
 Diffuse axonal injury may occur due to mechanical stretching or calcium influx with subsequent microtubule breakdown. Axonal bulbs may result due to intra-axonal cytoskeletal injury, accumulation of organelles at the site of damage axonal damage with localized axonal swellings appearing (axonal bulbs). Secondary axonotomy (constrictions) with axonal disconnection may occur many weeks after TBI.