Chemical and biochemical oxidations in spinal fluid after subarachnoid hemorrhage

Abstract

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.

Simvastatin Re-Couples Dysfunctional Endothelial Nitric Oxide Synthase in Experimental Subarachnoid Hemorrhage

“…SAH induces perivascular oxidative reactions probably mainly due to oxidation of extravascular hemoglobin [12], [13]. We found that SAH increased O 2 Γ and ONOOΓ production and iNOS expression, all of which may contribute to uncoupling of eNOS [6].…”

“…Retrospective studies reported mixed results, with three studies finding an increased risk of vasospasm or minimal effect in statin-treated patients [11], [13], [41], [42] and three primary studies reporting a marked reduction in vasospasm[43] [17], [44] and a metaanalysis confirming the observed trend of vasospasm reduction[45]. Additionally, two reported improved short-term clinical outcome and decreased mortality, respectively [44], [46].…”

Microglia inflict delayed brain injury after subarachnoid hemorrhage

“…Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH. spreading depolarisations (CSD), toxic effects of hemoglobin metabolites, microthromboembolism and the role of the blood brain barrier (BBB) have been discussed [14,19,48,64,66]. Inflammatory changes (i.e., an activation of innate immunity) have also been hypothesized as possible contributor to secondary brain injury, predisposal for cerebral vasospasm or aneurysm formation and rupture within the past years [13,28,53,55,68].…”

Hemolysate-induced Expression of Intercellular Adhesion Molecule-1 and Monocyte Chemoattractant Protein-1 Expression in Cultured Brain Microvascular Endothelial Cells via Through ROS-dependent NF-κB Pathways

“…Involvement of oxidative stress in the development of SAH was suggested by demonstrating the presence of increased protein and lipid peroxidation in the brain and cerebrospinal fluid (Liu et al 2007;Clark et al 2008). Previous results demonstrated that hemolysate has been shown to induce oxidative stress directly and indirectly (Yoshida et al 1994;Matz et al 2000).…”