Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.

Connolly, E. Sander; Winfree, Christopher J.; Springer, Timothy A.; Naka, Yoshifumi; Liao, Hui; Yan, Shirley ShiDu; Stern, David M.; Solomon, Robert A.; Gutierrez‐Ramos, José Carlos; Pinsky, David J.

doi:10.1172/jci118392

Cited by 483 publications

(288 citation statements)

References 56 publications

(48 reference statements)

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“…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). Finally, adhesion molecule knockout mice consistently exhibit smaller lesion volumes following focal stroke than their wild-type counterparts (Prestigiacomo et al, 1999;Soriano et al, 1996).…”

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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“…Treatment with an antibody specific for ICAM-1 has a similar effect, reducing inflammation and brain damage [10]. Furthermore, homozygous ICAM-1-deficient mice showed a 3·1-fold increase in blood flow in the infarcted hemisphere, a 3·7-fold reduction in infarct volume, a 35% increase in survival and reduced neurologic deficit compared with wild-type controls.…”

Section: Introductionmentioning

confidence: 87%

Intrathecal release of pro- and anti-inflammatory cytokines during stroke

Tarkowski

Rosengren

Blomstrand

et al. 1997

Clinical and Experimental Immunology

197

151

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SUMMARYA growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1b and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocytemacrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-a) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

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“…The administration of specific antibodies directed against ICAM-1 significantly reduced neutrophil accumulation, edema formation, infarction size, and neurologic damage after transient middle cerebral artery occlusion in rats (Bowes et al, 1993;Matsuo et al, 1994;Zhang et al, 1994). In ICAM-1 knockout mice, infarct volume and neurologic deficits were markedly reduced after focal cerebral ischemia, and survival was significantly prolonged in comparison with ICAM-1 +/+ animals (Connolly et al, 1996). An (Stocker et al, 1995 (Reiber and Felgenhauer, 1987 day 9, persisting to the end of the study period, whereas in group B there was only a transient elevation between days 9 and 13, followed by a rapid decrease to normal ranges (Fig.…”

Section: Introductionmentioning

confidence: 91%

Soluble ICAM-1 in CSF Coincides with the Extent of Cerebral Damage in Patients with Severe Traumatic Brain Injury

Pleines¹,

Stover²,

Kossmann³

et al. 1998

Journal of Neurotrauma

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Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.

Cited by 483 publications

References 56 publications

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia

Intrathecal release of pro- and anti-inflammatory cytokines during stroke

Soluble ICAM-1 in CSF Coincides with the Extent of Cerebral Damage in Patients with Severe Traumatic Brain Injury

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