Heme regulation in traumatic brain injury: relevance to the adult and developing brain.
Intracranial bleeding is one of the most prominent aspects in the clinical diagnosis and prognosis of traumatic brain injury (TBI). Substantial amounts of blood products, such as heme, are released because of traumatic subarachnoid hemorrhages, intraparenchymal contusions, and hematomas. Despite this, surprisingly few studies have directly addressed the role of blood products, in particular heme, in the setting of TBI. Heme is degraded by heme oxygenase (HO) into three highly bioactive products: iron, bilirubin, and carbon monoxide. The HO isozymes, in particular HO-1 and HO-2, exhibit significantly different expression patterns and appear to have specific roles after injury. Developmentally, differences between the adult and immature brain have implications for endogenous protection from oxidative stress. The aim of this paper is to review recent advances in the understanding of heme regulation and metabolism after brain injury and its specific relevance to the developing brain. These findings suggest novel clinical therapeutic options for further translational study.
Chang
Edward F
EF
Department of Neurosurgery, University of California, San Francisco, San Francisco, California 94143-0520, USA.
Claus
Catherine P
CP
Vreman
Hendrik J
HJ
Wong
Ronald J
RJ
Noble-Haeusslein
Linda J
LJ
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001921:Brain / Q000196:embryology* / Q000473:pathology; D002248:Carbon Monoxide / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D011379:Prognosis; D051381:Rats; D020206:Subarachnoid Hemorrhage, Traumatic / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology / Q000628:therapy
D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; D001663:Bilirubin