Figure 1.

Cellular pathways altered by traumatic brain injury in the juvenile brain. (1) Mechanical movement of the brain tissue causes massive depolarization of neurons. The indiscriminate release of neurotransmitters opens postsynaptic receptors and intermembrane ion concentrations are disrupted as ions flow down their concentration gradients. Na⁺and Ca⁺⁺ accumulates in the cells. Energy demanding ATPase pumps are activated to return ionic homeostasis. (2) Calcium accumulation is managed by calcium binding proteins and sequestration into mitochondria after TBI. (3) Changes in mitochondrial electron transport enzyme activities after TBI contribute to acute decrease ATP production and increase in reactive oxygen species production. The slower maturing anti-oxidant systems contribute to younger age vulnerabilities. (4) Metabolism induced oxygen free radicals form along the electron transport chain. Maturational lower levels of mitochondrial superoxide dismutase (SOD) and antioxidant enzyme glutathione peroxidase (GPx) along with the younger brain's lessened upregulation after TBI limit their capacity for reactive oxygen species management. This contributes to the oxidative stress of the cells. (5) After TBI, neurons release damage-associated molecular patterns (DAMPs), which induce morphological changes in astrocytes and microglia. In their activated states, microglia release cytokines and chemokines and astrocytes can inhibit microglial signaling and generate glial scarring that then contribute to the inflammatory cascades post injury.