Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons.

Zoppo, Gregory J. del; Schmid‐Schönbein, Geert W.; Mori, Etsuro; Copeland, Brian R.; Chang, Cheng‐Ming

doi:10.1161/01.str.22.10.1276

Cited by 667 publications

(438 citation statements)

References 22 publications

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“…Although not a universal finding (Hayward et al, 1996;Emerich et al, 2002), considerable evidence supports the notion that adherent and infiltrating leukocytes contribute to ischemic damage following focal ischemia (see Jean et al, 1998 andWang et al, 2005 for reviews). In particular, the degree of leukocyte infiltration following focal stroke correlates with the severity of neuronal injury and neurological deficits in animals Clark et al, 1994;del Zoppo et al, 1991) and humans (Akopov et al, 1996). Moreover, in focal ischemia models, anti-leukocyte interventions decrease cerebral edema (Strachan et al, 1992), improve cerebral blood flow (Grogaard et al, 1989;Connolly et al, 1996;Ishikawa et al, 2004), and reduce infarct size (Connolly et al, 1996;Chopp et al, 1994;Beech et al, 2001;Xu et al, 2004;Zheng et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Altay

McLaughlin

et al. 2007

Experimental Neurology

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Cerebrovascular inflammation contributes to secondary brain injury following ischemia. Recent in vitro studies of cell migration and molecular guidance mechanisms have indicated that the Slit family of secreted proteins can exert repellant effects on leukocyte recruitment in response to chemoattractants. Utilizing intravital microscopy, we addressed the role of Slit in modulating leukocyte dynamics in the mouse cortical venular microcirculation in vivo following TNFα application or global cerebral ischemia. We also studied whether Slit affected neuronal survival in the mouse global ischemia model as well as in mixed neuronal-glial cultures subjected to oxygenglucose deprivation. We found that systemically administered Slit significantly attenuated cerebral microvessel leukocyte-endothelial adherence occurring 4 h after TNFα and 24 h after global cerebral ischemia. Administration of RoboN, the soluble receptor for Slit, exacerbated the acute chemotactic response to TNFα. These findings are indicative of a tonic repellant effect of endogenous Slit in brain under acute proinflammatory conditions. Three days of continuous systemic administration of Slit following global ischemia significantly attenuated the delayed neuronal death of hippocampal CA1 pyramidal cells. Moreover, Slit abrogated neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation. The ability of Slit to reduce the recruitment of immune cells to ischemic brain and to provide cytoprotective effects suggests that this protein may serve as a novel anti-inflammatory and neuroprotective target for stroke therapy.

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Section: Discussionmentioning

confidence: 99%

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Altay

McLaughlin

et al. 2007

Experimental Neurology

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“…In the periphery, neutrophils are the first circulating leukocytes to arrive at the site of injury. When they accumulate in blood vessels, neutrophils may bring about a reduction in blood flow and occlusion of microvessels (del Zoppo et al, 1991). The release of lysosomal enzymes and free radicals by neutrophils also produces an increase in vascular permeability, which gives rise to edema (Weiss, 1989).…”

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confidence: 99%

Recruitment of Neutrophils across the Blood–Brain Barrier: The Role of E- and P-selectins

Bernardes-Silva

Anthony²,

Issekutz

et al. 2001

J Cereb Blood Flow Metab

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Summary:The adult central nervous system parenchyma is resistant to inflammation, but in juvenile rats the injection of inflammatory mediators, interleukin-1␤ for example, gives rise to extensive neutrophil recruitment and neutrophil-dependent blood-brain barrier breakdown. The factors that confer this resistant phenotype are unknown. In this study, the authors demonstrate that E-and P-selectin expression is increased to a similar extent in adult and juvenile brain after the intracerebral injection of IL-1␤. Thus, the refractory nature of the brain parenchyma cannot be attributed to an absence of selectin expression. However, in injuries where the resistant characteristic of the brain parenchyma is compromised, and neutrophil recruitment occurs, selectin blockade may be an advantage. The authors investigated the contribution that selectins make to neutrophil recruitment during acute inflammation in the brain. The authors examined neutrophil recruitment by immunohistochemistry on brain sections of juvenile rats killed four hours after the intracerebral injection of IL-1␤ and the intravenous injection of neutralizing anti-selectin monoclonal antibodies (mAb). The administration of the P-selectin blocking mAb inhibited neutrophil recruitment by 85% compared with controls. Surprisingly, E-selectin blockade had no effect on neutrophil recruitment to the brain parenchyma. Thus, P-selectin appears to play a pivotal role in mediating neutrophil recruitment to the brain parenchyma during acute inflammation.

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“…1,2 Various mechanisms have been proposed including enhanced production of inflammatory mediators, [3][4][5] recruitment of polymorphonuclear leukocytes (PMN), 6,7 and blockage of blood flow. [7][8][9] The leukocyte-endothelial interaction that occurs following ischemia/reperfusion (I/Rp) injury has been shown to be important for microvascular dysfunction and release of cytotoxic mediators such as reactive oxygen intermediates and a variety of proteases. [10][11][12] We 13 and others 5,6,9,14,15 have shown leukocyte accumulation to be a critical determinant of hepatic I/Rp injury.…”

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confidence: 99%

P–Selectin Mediates Reperfusion Injury Through Neutrophil and Platelet Sequestration in the Warm Ischemic Mouse Liver

Yadav¹,

et al. 1999

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Hepatic damage following ischemia-reperfusion injury involves polymorphonuclear leukocytes (PMN) and platelet sequestration, however the mechanisms of adhesion remain elusive. In this study, using gene-targeted deficient mice, we evaluated P-selectin and its contribution to PMN and platelet adhesion in hepatic damage. In an in vivo warm ischemia model, hepatic injury was assessed by serum transaminase levels, survival, PMN adhesion by histological analysis, and platelet sequestration by immunostaining. Serum transaminase levels were strikingly reduced (by up to threefold) in the P-selectin deficient mice, particularly at 90 minutes of ischemia, when compared with wild-type controls. PMN adhesion and platelet sequestration was also significantly decreased in P-selectin deficient mice following 90 minutes of partial ischemia. Animal survival was significantly improved after 75 minutes of total hepatic ischemia in P-selectin deficient mice when compared with wild-type mice. Survival was also achieved after 90 minutes of ischemia in the mutant mice whereas none of the wild-type animals survived. These data show that P-selectin plays a critical role in PMN and platelet adhesion following ischemia-reperfusion injury to the liver. (HEPATOLOGY 1999; 29:1494-1502.)The pathogenesis of cell damage following reperfusion of ischemic tissue is an incompletely understood series of events. 1,2 Various mechanisms have been proposed including enhanced production of inflammatory mediators, 3-5 recruitment of polymorphonuclear leukocytes (PMN), 6,7 and blockage of blood flow. 7-9 The leukocyte-endothelial interaction that occurs following ischemia/reperfusion (I/Rp) injury has been shown to be important for microvascular dysfunction and release of cytotoxic mediators such as reactive oxygen intermediates and a variety of proteases. 10-12 We 13 and others 5,6,9,14,15 have shown leukocyte accumulation to be a critical determinant of hepatic I/Rp injury. Other blood elements including platelets adhere to the hepatic sinusoids in conditions of ischemia, 16,17 but little is known about their contribution to the injury.The adhesion of PMN and platelets to the vascular endothelium involves a variety of adhesion receptors. [18][19][20][21] The selectin family (P-, E-, and L-selectin) are the first to be engaged in the process, 19 with P-selectin acting at the earliest stage of interaction between PMN and the endothelium. P-selectin is found in the ␣ granules of resting platelets and Weibel-Palade bodies of endothelial cells, 18 and expression of P-selectin on the cell surface can occur within minutes under stimulation by mediators of inflammation such as thrombin, histamine, complement, and peroxide. 22 P-selectin is able to tether leukocytes to the endothelial surface through its ligand P-selectin glycoprotein ligand-1 (PSGL-1), which leads to their activation. 23 Once leukocytes attach, they can interact with flowing PMN and platelets through the action of P-and L-selectin, 23 which may lead to further adhesion of PMN and platelets as we...

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Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons.

Cited by 667 publications

References 22 publications

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Recruitment of Neutrophils across the Blood–Brain Barrier: The Role of E- and P-selectins

P–Selectin Mediates Reperfusion Injury Through Neutrophil and Platelet Sequestration in the Warm Ischemic Mouse Liver

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