Oxyhemoglobin-induced apoptosis in cultured endothelial cells

Ogihara, Kotaro; Zubkov, Alexander Y.; Bernanke, David H.; Lewis, Adam I.; Parent, Andrew D.; Zhang, Junyi

doi:10.3171/jns.1999.91.3.0459

Cited by 58 publications

(31 citation statements)

References 29 publications

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“…The degree of cytotoxicity was related to the concentrations of Hb over time (72). Other studies have shown similar effects associated with DNA damage and apoptosis (73,74).…”

Section: Hb Toxicity Towards Endothelial Cellsmentioning

confidence: 60%

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

Sercombe

Dinh

Gomis

2002

Japanese Journal of Pharmacology

184

140

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ABSTRACT-Aneurysmal subarachnoid hemorrhage frequently results in complications including intracranial hypertension, rebleeding and vasospasm. The extravasated blood is responsible for a cascade of reactions involving release of various vasoactive and pro-inflammatory factors (several of which are purported to induce vasospasm) from blood and vascular components in the subarachnoid space. The authors review the available evidence linking these factors to the development of inflammatory lesions of the cerebral vasculature, emphasizing: 1) neurogenic inflammation due to massive release of sensory nerve neuropeptides; 2) hemoglobin from lysed erythrocytes, which creates functional lesions of endothelial and smooth muscle cells; 3) activity, expression and metabolites of lipoxygenases cyclooxygenases and nitric oxide synthases; 4) the possible role of endothelin-1 as a pro-inflammatory agent; 5) serotonin, histamine and bradykinin which are especially involved in blood-brain barrier disruption; 6) the prothrombotic and pro-inflammatory action of complement and thrombin towards endothelium; 7) the multiple actions of activated platelets, including platelet-derived growth factor production; 8) the presence of perivascular and intramural macrophages and granulocytes and their interaction with adhesion molecules; 9) the evolution, origins, and effects of pro-inflammatory cytokines, especially IL-1, TNF-a and IL-6. Human and animal studies on the use of anti-inflammatory agents in subarachnoid hemorrhage include superoxide and other radical scavengers, lipid peroxidation inhibitors, iron chelators, NSAIDs, glucocorticoids, and serine protease inhibitors. Many animal studies claim reduced vasospasm, but these effects are not always confirmed in human trials, where symptomatic vasospasm and outcome are the major endpoints. Despite recent work on penetrating vessel constriction, there is a paucity of studies on inflammatory markers in the microcirculation.

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“…The degree of cytotoxicity was related to the concentrations of Hb over time (72). Other studies have shown similar effects associated with DNA damage and apoptosis (73,74).…”

Section: Hb Toxicity Towards Endothelial Cellsmentioning

confidence: 60%

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

Sercombe

Dinh

Gomis

2002

Japanese Journal of Pharmacology

184

140

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“…It has also been shown that oxyhemoglobin can induce apoptosis in cultured endothelial cells, possibly through free radical damage to the endothelial vessel wall tissue. 9 The temporal pattern of edema formation after infusion of lysed or packed erythrocytes is similar to the pattern of BBB disruption. 3 A second mechanism that might contribute to edema development after erythrocyte lysis is direct damage to neurons and astrocytes involved in maintaining extracellular homeostasis.…”

Section: Discussionmentioning

confidence: 72%

Mechanisms of Edema Formation After Intracerebral Hemorrhage

Hua

Bhasin

et al. 2001

Stroke

178

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Background and Purpose-Red blood cell (RBC) lysis contributes to brain edema formation after intracerebral hemorrhage (ICH), and RBC hemolysate (oxyhemoglobin) has been implicated to be a spasminogen in subarachnoid hemorrhage. Whether cerebral ischemia contributes to brain edema formation after ICH remains unclear, however. The aims of this study were to test whether extravasation of RBCs induces cerebral ischemia and/or blood-brain barrier disruption in a rat ICH model characterized by perihematomal brain edema. Methods-In this study, 87 pentobarbital-anesthetized Sprague-Dawley rats were used. In each animal, saline, packed RBCs, or lysed RBCs were injected into the right caudate nucleus. Sham injections served as controls. Regional cerebral blood flow, brain water and ion contents, blood-brain barrier integrity, and plasma volume were measured. Results-Intraparenchymal infusion of lysed RBCs caused severe brain edema by the first day but did not induce ischemic cerebral blood flows. In contrast, blood-brain barrier permeability increased during the first day after infusion of lysed RBCs (a 3-fold increase) and 3 days after infusion of packed RBCs (a 4-fold increase). Conclusions-These results suggest that ischemia is not present at 24 or 72 hours after hematoma induction by injection of intact or lysed RBCs. RBC constituents that appear after delayed lysis, however, increase blood-brain barrier permeability, which contributes to edema formation. (Stroke. 2001;32:2932-2938.)

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“…Damage to the vascular endothelium may be because of oxidative stress perpetuated by iron (Ogihara et al, 1999;Wu et al, 2003Wu et al, , 2002 and furthermore the administration of iron chelators attenuates edema after intracerebral hemorrhage (Huang et al, 2002).…”

Section: Heme Oxygenase As Modulator Of Neural Injurymentioning

confidence: 99%

Heme Regulation in Traumatic Brain Injury: Relevance to the Adult and Developing Brain

Chang

Claus

Vreman

et al. 2005

J Cereb Blood Flow Metab

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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.

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Oxyhemoglobin-induced apoptosis in cultured endothelial cells

Cited by 58 publications

References 29 publications

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

Cerebrovascular Inflammation Following Subarachnoid Hemorrhage

Mechanisms of Edema Formation After Intracerebral Hemorrhage

Heme Regulation in Traumatic Brain Injury: Relevance to the Adult and Developing Brain

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