Chemical and biochemical oxidations in spinal fluid after subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a stroke with high rates of mortality and morbidity. SAH-induced cerebral vasospasm can lead to ischemic injury or death and is a common complication of SAH. Recently there has been an accumulation of emerging evidence that oxidation of heme-derived bilirubin into bilirubin oxidation products (BOXes) may be involved in cerebral vasospasm. BOXes are produced by the oxidation of bilirubin yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl- (1,5-dihydropyrrol-2-ylidene)acetamide (BOX B). BOXes have been a subject of interest in the neurosurgical and neurological fields for several years because of their purported correlation with and or role in subarachnoid hemorrhage induced cerebral vasospasm. We believe that it is critical to understand the chemical and biochemical environment in the hemorrhagic spinal fluid after SAH that leads to the oxidation of bilirubin. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes.