Pathophysiological events resulting in blood–brain barrier breakdown and development of cerebral edema following burn injury. Following major burn trauma, a robust systemic inflammatory response is triggered. Proinflammatory mediators are produced by various immune cells, resulting in breakdown of the blood–brain barrier, with subsequent activation of resident central nervous system cells, such as microglia and astrocytes, which respond with further production of inflammatory markers, cumulating in a massive neuroinflammatory response and subsequent life-threatening cerebral edema. In parallel, significant hormonal changes are triggered, resulting in a severe hypermetabolic state. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic hormone.