The pathophysiology of brain death is primarily related to the secondary effects of long-standing brain edema.
The inciting event is an injurious event to the brain, such as a traumatic or cerebrovascular insult which will then lead to generalized hypoxia and resultant brain edema through either vasogenic (causing disruption of the BBB and increased leakage of protein into brain) or cytotoxic (intact BBB but increased entry of water into brain) mechanisms.
Brain edema may be focal at first, but it then spreads throughout the whole brain in a predictable sequence. Because the brain is encased by the skull, edema will invariably lead to an increase in ICP which, if high enough can exceed arterial blood pressure and decrease cerebral blood flow.
When CBF ceases, the brain begins to die through a process known as aseptic necrosis. Within 3-5 days, the brain becomes liquefied and is often referred to as “respirator brain” (1). Such increased intracranial pressure compresses the entire brain and brainstem and total brain infarction soon follows.
A E Walker, E L Diamond, J Moseley The neuropathological findings in irreversible coma. A critque of the “respirator”. J. Neuropathol. Exp. Neurol.: 1975, 34(4);295-323