Hu23F2G, an Antibody Recognizing the Leukocyte CD11/CD18 Integrin, Reduces Injury in a Rabbit Model of Transient Focal Cerebral Ischemia

Yenari, Midori A.; Kunis, David M.; Sun, Guo Hua; Onley, David J.; Watson, Linda; Turner, Stephanie D.; Whitaker, Steven; Steinberg, Gary K.

doi:10.1006/exnr.1998.6876

Cited by 108 publications

(73 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies in the absence of a systemic inflammatory stimulus, in which neutrophils have been depleted or their emigration from the vasculature inhibited, have provided considerable evidence that neutrophils contribute to ischemic brain damage (Chen et al, 1994;Connolly et al, 1996;Dawson et al, 1996;Yenari et al, 1998;Beray-Berthat et al, 2003;Arumugam et al, 2004), although there are also conflicting reports (Fassbender et al, 2002;Maier et al, 2004). In the present study, IL-1␤ potentiated the postischemic neutrophilia and accumulation of neutrophils in the cerebral cortex before alterations in brain damage.…”

Section: Discussionsupporting

confidence: 47%

“…Such a temporal and spatial pattern is consistent with a causative role in the development of enhanced cortical injury and this was supported by the marked attenuation of IL-1␤-induced cortical damage by neutrophil depletion. Indeed, the contribution of neutrophils to brain damage appears to be brain region specific with a predominant role in the cortex (Yenari et al, 1998;BerayBerthat et al, 2003). This may reflect the more extensive vasculature and greater perfusion of cortical tissue (cf.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms

McColl¹,

Rothwell

Allan³

2007

J. Neurosci.

317

339

View full text Add to dashboard Cite

Systemic inflammatory stimuli, such as infection, increase the risk of stroke and are associated with poorer clinical outcome. The mechanisms underlying the impact of systemic inflammatory stimuli on stroke are not well defined. We investigated the impact of systemic inflammation on experimental stroke and potential mechanisms involved. Focal cerebral ischemia was induced by intraluminal filament occlusion of the middle cerebral artery (MCAo). Brain damage and neurological deficit 24 h after MCAo were exacerbated by systemic lipopolysaccharide (LPS) administration. This exacerbation was critically dependent on interleukin (IL)-1, because coadministration of IL-1 receptor antagonist abolished the effect of LPS on brain damage. Systemic administration of IL-1 increased ischemic damage to a similar extent as LPS and also exacerbated brain edema. IL-1 markedly potentiated circulating levels of the acute phase proteins, serum amyloid A and IL-6, and the neutrophil-selective CXC chemokines, KC and macrophage inflammatory protein-2. Neutrophil mobilization and cortical neutrophil infiltration were aggravated by IL-1 before changes in ischemic damage. Neutropenia abolished the damaging effects of systemic IL-1. These data show for the first time that an acute systemic inflammatory stimulus is detrimental to outcome after experimental stroke and highlight IL-1 as a critical mediator in this paradigm. Our data suggest IL-1-induced potentiation of neutrophil mobilization via CXC chemokine induction is a putative mechanism underlying this effect. Our results may help to explain the poorer outcome in stroke patients presenting with infection and may have implications for neurodegenerative diseases involving neurovascular alterations, such as Alzheimer's disease, in which systemic inflammation can modulate disease progression.

show abstract

Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms

McColl¹,

Rothwell

Allan³

2007

J. Neurosci.

317

339

View full text Add to dashboard Cite

show abstract

“…Yet the pathogenic role of neutrophils after cerebral ischemia and reperfusion remains uncertain, with some studies failing to show a clear correlation between neutrophil infiltration and infarct formation (Beray-Berthat et al, 2003b;Emerich et al, 2002;Fassbender et al, 2002;Hayward et al, 1996;Soriano et al, 1999;Takeshima et al, 1992). Furthermore, the role of neutrophils after cerebral ischemia is made more complex by recent studies that have reported variability in the extent of ischemic injury associated with neutrophil infiltration, between cerebral regions, including the cortex and striatum (Batteur-Parmentier et al, 2000;Beray-Berthat et al, 2003a, b;Kitagawa et al, 1998;Yenari et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cell Infiltration after Endothelin-1-Induced Cerebral Ischemia: Histochemical and Myeloperoxidase Correlation with Temporal Changes in Brain Injury

Weston

Jones

Jarrott

et al. 2007

J Cereb Blood Flow Metab

128

View full text Add to dashboard Cite

Accumulation of neutrophils in brain after transient focal stroke remains controversial with some studies showing neutrophils to be deleterious, whereas others suggest neutrophils do not contribute to ischemic injury. Myeloperoxidase (MPO) has been used extensively as a marker for quantifying neutrophil accumulation, but is an indirect method and does not detect neutrophils alone. To elucidate the interaction of macrophages in the neutrophil inflammatory response, we conducted double-label immunofluorescence in brain sections at 0, 1, 2, 3, 7, and 15 days after ischemia. Each of these results was obtained from the same animal to determine correlations between neutrophil infiltration and ischemic damage. It was found that MPO activity increased up to 3 days after cerebral ischemia. Dual-staining revealed that macrophages engulf neutrophils in the brain and that this engulfment of neutrophils increased with time, with 50% of neutrophils in the brain engulfed at 3 days and approximately 85% at 15 days (N = 5, P < 0.05). Interestingly, at 7 days the amount of dual-staining was decreased to 20% (N = 5, P < 0.05). Neutrophil infiltration was positively correlated with ischemic damage in both the cortex and striatum (r 2 = 0.86 and 0.80, respectively, P < 0.01). The results of this study indicate that the MPO from neutrophils phagocytized by macrophages may continue to contribute to the overall MPO activity, and that previous assessments that have utilized this marker to measure neutrophil accumulation may have miscalculated the number of neutrophils within the ischemic territory and hence their contribution to the evolution of the infarct at later time points. Thus any biphasic infiltration of neutrophils may have been masked by the accumulation of macrophages.

show abstract

“…Monoaminergic system Dopamine receptor agonists [51,52] Inhibition of ischemia-induced norepinephrine release [53] 5-HT receptors agonists [54] γ-GABA [55,56] Adenosine agonists [57] Therapeutic hypothermia [1] Calcium-channel antagonism [58] N-voltage sensitivity calcium channel (VSCC) antagonists [59] L-voltage sensitivity calcium channel (VSCC) antagonists [60] Ionotropic glutamate receptor (IGRC) [58] Calcium-permeable acid-sensing ion channels (ASICs) antagonists [61] Sodium-channel antagonism/blockade of glutamate release [44] Potassium channel opener [62] Antagonism of free radicals Superoxide dismutase, catalase [63] 21-aminosteroids [64,65] Free radical scavengers: [ 66,67] Spin-trap agents [68] Agents affecting nitric oxide: statins [69] , aminoguanidine [12] , minocycline [70] Inhibition of cytoskeletal (spectrin) proteolysis [71] Antagonism of neutrophil activation or binding [72] Anti-CD11b or CD18 monoclonal antibody [73] Immunosuppressive agents [74][75][76][77][78] Inhibition of astrocyte activity A2A adenosine receptor antagonisms [79,80] Cytokine receptor antagonists [4] Neurotrophic factors [81] Human albumin [1] Agents of anti-apoptosis [82] Ovarian hormones [83] Anesthetic agents: isoflurane …”

Section: Pharmacological Treatments To Alleviate the Molecular Injurymentioning

confidence: 99%

“…However, neuroprotection may contribute to the temporary preservation of the penumbra, bridging the interval between the onset of ischemia and the restitution of blood flow, and/or preventing secondary neuronal death during reperfusion. These interventions include approaches of anti-excitotoxicity, anti- Competitive [44,45] Noncompetitive [44,46,47] Glycine-site [48] Non-NMDA (AMPA/Kainic acid receptor) antagonists [49] Cannabinoids [50] (antagonism of NMDA, AMPA and kainic acid receptor)Agents affecting nonglutamatergic neurotransmissionMonoaminergic system Dopamine receptor agonists [51,52] Inhibition of ischemia-induced norepinephrine release [53] 5-HT receptors agonists [54] γ-GABA [55,56] Adenosine agonists [57] Therapeutic hypothermia [1] Calcium-channel antagonism [58] N-voltage sensitivity calcium channel (VSCC) antagonists [59] L-voltage sensitivity calcium channel (VSCC) antagonists [60] Ionotropic glutamate receptor (IGRC) [58] Calcium-permeable acid-sensing ion channels (ASICs) antagonists [61] Sodium-channel antagonism/blockade of glutamate release [44] Potassium channel opener [62] Antagonism of free radicals Superoxide dismutase, catalase [63] 21-aminosteroids [64,65] Free radical scavengers: [ 66,67] Spin-trap agents [68] Agents affecting nitric oxide: statins [69] , aminoguanidine [12] , minocycline [70] Inhibition of cytoskeletal (spectrin) proteolysis [71] Antagonism of neutrophil activation or binding [72] Anti-CD11b or CD18 monoclonal antibody [73] Immunosuppressive agents …”

mentioning

confidence: 99%

The mechanisms of brain ischemic insult and potential protective interventions

Guo

Wang

2009

Neurosci. Bull.

View full text Add to dashboard Cite

Abstract:The mechanisms of brain ischemic insult include glutamate excitoxicity, calcium toxicity, free radicals, nitric oxide, inflammatory reactions, as well as dysfunctions of endoplasmic reticulum and mitochondrion. These injury cascades are interconnected in complex ways, thus it is hard to compare their pathogenic importances in ischemia models. And the research in cellular and molecular pathways has spurred the studies in potential neuroprotections mainly in pharmacological fields, such as anti-excitotoxic treatment, calcium-channel antagonism, approaches for inhibition of oxidation, inflammation and apoptosis, etc. Besides, other protective interventions including thrombolysis, arteriogenesis, regeneration therapy, and ischemia preconditioning or postconditioning, are also under investigations. Despite the present difficulties, we are quite optimistic towards future clinical applications of neuroprotective agents, by optimizing experimental approaches and clinical trials.Key words: brain ischemia; glutamate receptors; calcium toxicity; endoplasmic reticulum stress; neuroprotection 1 Brain ischemia 1.1 Definition What's brain ischemia? Is it the reduction of cerebral blood flow (CBF)? The answer is "No". The analysis of the correlation between early local blood flow and histological infarct frequency showed that the likelihood of infarction was at zero [1] or low (probably less than 5%) [2] in animals or patients, respectively, when early CBF remained above 50% of that in control.During the initial hours of vascular occlusion, the metabolic and ionic disturbances in the periphery of focal ischemia proceed at widely varying flow thresholds ( Fig.1) in the following order: firstly protein synthesis is inhibited at a threshold of about 0.55 mL/(g·min) followed by a stimulation of anaerobic glycolysis below 0.35 mL/(g·min), a breakdown of energy state at about 0.20 mL/(g·min) and anoxic depolarizations of the cell membranes below 0.15 mL/(g·min) [3] .The two different thresholds of hypoxia for the preservations of functional and structural integrities were identified by Symon et al. [4] . The higher threshold is at approximately 35% of normal CBF, and the lower one is at approximately 25-20% of normal ( Fig.1). The ischemic penumbraLike a half-shaded zone surrounding a solar eclipse, the penumbra lies peripherally to the core zone of a focal ischemic lesion, and possesses important features: summarily, the substantial initial size, which amounts to about one half of the entire early ischemic lesion; the narrow range of perfusion, which makes the penumbra precariously sensitive to small changes of perfusion pressure; the electrophysiologically dynamic property, which enables penumbra to undergo recurrent energy-consuming depolarizations ; and finally the metabolical instability with severe metabolism/flow dissociation.As a result of these factors, the penumbra clearly has a limited life span and appears to undergo irreversible injury within a few hours unless reperfusion is initiated and/or 140 Neurosci Bull J...

show abstract

Hu23F2G, an Antibody Recognizing the Leukocyte CD11/CD18 Integrin, Reduces Injury in a Rabbit Model of Transient Focal Cerebral Ischemia

Cited by 108 publications

References 32 publications

Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms

Systemic Inflammatory Stimulus Potentiates the Acute Phase and CXC Chemokine Responses to Experimental Stroke and Exacerbates Brain Damage via Interleukin-1- and Neutrophil-Dependent Mechanisms

Inflammatory Cell Infiltration after Endothelin-1-Induced Cerebral Ischemia: Histochemical and Myeloperoxidase Correlation with Temporal Changes in Brain Injury

The mechanisms of brain ischemic insult and potential protective interventions

Contact Info

Product

Resources

About