Brain Trauma

There are two forms of brain injury - mechanical (physical disruption of vessels and axons and direct axonal shearing) and ischemic injury.

Physical (mechanical) Mechanisms of Injury

Head injury produces a negative or positive acceleration of the brain with respect to the surrounding skull or connective tissue (falx cerebri or tentorium cerebelli). There are 2 types of mechanical injury - COUP and CONTRECOUP injury. Initially, there is a transient deformation of the calvarium by an external force, which results in either a compression skull fracture or a springing of the bones back into normal position. This produces the COUP injury. The resultant pressure waves then can produce contusions or transient brain herniation at sites distant from the area of impact, which represents the CONTRACOUP injury. As a result, widespread and distant areas of hemorrhage can occur in the epidural, subdural or subarachnoid spaces (via stretching and/or tearing of vessels); within the parenchyma (most common in animals); and in the mesencephalon and pons (from sudden, very high increases in intracranial pressure).

Ischemic Mechanisms of Injury

Over a number of hours to days post brain trauma, there can be progressive ischemic brain injury. Extreme energy failure leads to cell death. However, in many cases, there is a modest energy compromise, which will lead to neurotoxicity via increases in intracellular and extracellular glutamate; N-methyl D-aspartate (NMDA) receptor activation; and increases in intracellular calcium. This in turn leads to overstimulation of protein kinases, phospholipases, proteases, protein phosphatases, xanthine oxidase, and nitric oxide synthase inside the cell. The end result is protein and lipid breakdown (phospholipid hydrolysis); release of arachidonic acid; free radical and eicosanoid formation; ATP depletion, and eventually, cell death. Ischemic cell injury also leads to cerebral edema.

Cerebral Edema

Brain edema plus hematoma formation, are the major causes of delayed brain damage. There are 2 types of edema: vasogenic, which is secondary to increased vascular permeability (physical mechanisms of injury); and cytotoxic edema, which is secondary to hypoxia/ ischemia & impaired cellular metabolism. Edema and hematoma lead to increased intracranial pressure.

Increased Intracranial Pressure

When the total volume of material within the cranium is increased by edema, hematoma, & bone fragments, CSF and venous blood exit to compensate. However, the sudden increase in compartment volume can exceed these compensatory limits. Any small additional increases in volume produce very high increases in ICP since compliance is low. This results in brain herniation, as well as increases in mean arterial pressure, leading to increased systemic arterial peripheral resistance and neurogenic pulmonary edema. [...]