ABSTRACT
The pathophysiology of traumatic brain injury (TBI) involves dysfunction of various cerebral homeostatic mechanisms, resulting in alterations in cerebral blood flow (CBF), autoregulatory capacity, cerebral metabolism, and oxygenation in response to the biomechanical insult produced by trauma. The skull comprises a rigid compartment, which houses the brain; blood, and cerebrospinal fluid (CSF). The Monro–Kellie doctrine describes the dynamic equilibrium among the volumes of these three components in an intact skull. Factors controlling the intracranial pressure include intracranial compliance, CSF hydrodynamics, and cerebral hemodynamics. CBF is primarily dependent on the metabolic needs of the brain as reflected by flow-metabolism coupling in regional control of cerebral blood flow. Cerebral autoregulation maintains fairly constant CBF, despite changes in cerebral perfusion pressure. Autoregulation involves myogenic, metabolic, and neural mechanisms, along with added contributions from endothelial cell-related factors. TBI pathophysiology involves a series of events at biochemical and molecular levels, which invoke a dysregulation of normal cerebral physiology, which ensues a cascade of primary and secondary damage with a spectrum of flow-metabolism uncoupling, excitotoxicity, calcium, and lactate accumulation, edema, inflammation, and cell death.
