Reperfusion Injury after Focal Cerebral Ischemia: The Role Inflammation and the The rapeutic Horizon

Jean, Walter C.; Spellman, Stephen R.; Nussbaum, Eric S.; Low, Walter C.

doi:10.1097/00006123-199812000-00076

Cited by 108 publications

(39 citation statements)

References 163 publications

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“…16,17,25 Circulating factors have been shown to have a significant effect on BBB properties that could enhance the detrimental effects of I/R. 19 In the present study, we found that nonischemic arteries perfused with plasma from hyperglycemic MCAO animals did not significantly increase BBB permeability.…”

Section: Discussionsupporting

confidence: 44%

Inhibition of Protein Kinase Cβ Reverses Increased Blood–Brain Barrier Permeability During Hyperglycemic Stroke and Prevents Edema Formation In Vivo

Cipolla

Huang

Sweet

2011

Stroke

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Purpose We investigated the effect of circulating factors and protein kinase Cβ (PKCβ) on blood-brain barrier permeability and edema during hyperglycemic stroke. Methods Male Wistar rats that were hyperglycemic by streptozotocin (50 mg/kg) for 5–6 days underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Blood-brain barrier permeability was measured in MCAs that were ischemic (MCAO) or nonischemic (CTL) and perfused with plasma (20% in buffer) from MCAO or CTL animals. A separate set of MCAO vessels was perfused with the PKCβ inhibitor CGP53353 (0.5 μmol/L) and permeability measured. Lastly, hyperglycemic rats were treated i.v. with CGP53353 (10 or 100 μg/kg or vehicle 15 minutes prior to reperfusion and edema formation measured by wet:dry weights (n=6/group). Results MCAO vessels had increased permeability compared to controls, regardless of the plasma perfusate. Permeability (water flux, μm3 × 108) of CTL vessel/CTL plasma (n=8), CTL vessel/MCAO plasma (n=7), MCAO vessel/CTL plasma (n=6) and MCAO vessel/MCAO plasma (n=6) was 0.98±0.11, 1.13±0.07, 1.36±0.02, and 1.34±0.06; p<0.01). Inhibition of PKCβ in MCAO vessels (n=6) reversed the increase in permeability (0.92±0.1; p<0.01). In vivo, hyperglycemia increased edema vs. normoglycemia after MCAO (water content = 78.84±0.11% vs. 81.38±0.21%; p<0.01). Inhibition of PKCβ with 10 or 100 μg/kg CGP53353 during reperfusion prevented the increased edema in hyperglycemic animals (water content = 79.54±0.56% and 79.99±0.43%; p<0.01 vs. vehicle). Conclusions These results suggest that the pronounced vasogenic edema that occurs during hyperglycemic stroke is mediated in large part by activation of PKCβ.

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Section: Discussionsupporting

confidence: 44%

Inhibition of Protein Kinase Cβ Reverses Increased Blood–Brain Barrier Permeability During Hyperglycemic Stroke and Prevents Edema Formation In Vivo

Cipolla

Huang

Sweet

2011

Stroke

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“…In addition, an anti-CD11/CD18 antibody was employed within 12 hours after symptom onset [12, 83] in ischemia patients. However, both clinical trials failed, although they inhibited neutrophil aggregation and improved functional outcomes in animal studies [69, 84, 85]. The different expression profiles of integrin between human and animal stroke models may explain these failures.…”

Section: Adhesion Cascade In Cns Disordersmentioning

confidence: 99%

Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets

Ma¹,

Chen²,

Klebe³

et al. 2013

CNSNDDT

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Mounting evidence has been provided regarding the crucial role of leukocyte extravasation and subsequent inflammatory response in several central nervous system (CNS) disorders. The infiltrated leukocytes release pro-inflammatory mediators and activate resident cells, leading to tissue injury. Leukocyte-endothelia interaction is critical for leukocyte extravasation and migration from the intravascular space into the tissue during inflammation. The basic physiology of leukocyte-endothelia interaction has been investigated extensively. Traditionally, three kinds of adhesion molecules, selectin, integrin, and immunoglobulin families, are responsible for this multiple-step interaction. Furthermore, blocking adhesion molecule function by genetic knockout, antagonizing antibodies, or inhibitory pharmacological drugs provides neuroprotection, which is associated with a reduction in leukocyte accumulation with in the tissue. Detection of the soluble form of adhesion molecules has also been proven to predict outcomes in CNS disorders. Lately, vascular adhesion protein-1 (VAP-1), a novel adhesion molecule and endothelial cell surface enzyme, has been implicated as a brake during leukocyte extravasation. In this review, we summarize the functions of traditional adhesion molecules as well as VAP-1 in the leukocyte adhesion cascade. We also discuss the diagnostic and therapeutic potential of adhesion molecules in CNS disorders.

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“…Also, numerous studies have evaluated the effects of HBO on inflammatory reactions. Increases in activation and adhesion of leukocytes, especially neutrophils, have been well described after cerebral ischemia, and higher neutrophil counts have been associated with poor outcome [24,25,26]. Further, inhibition of neutrophil accumulation by blocking ICAM-1 [27,28,29]or using antineutrophil antibodies [28, 30 ]has been shown to decrease ischemic injury and limit postischemic apoptosis [31].…”

Section: Mechanism Of Action Of Hbomentioning

confidence: 99%

Hyperbaric Oxygen Therapy of Cerebral Ischemia

Helms

Whelan

Torbey³

2005

Cerebrovasc Dis

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Background: Hyperbaric oxygen (HBO) therapy of cerebral ischemia has been evaluated in a number of human and animal studies; however, there is presently no consensus on its efficacy. Methods: We present a review of animal and human studies on HBO therapy of cerebral ischemia as well as present potential mechanisms of action of HBO. Results: Animal studies of HBO have shown promise by reducing infarct size and improving neurologic outcome. HBO has also been shown to inhibit inflammation and apoptosis after cerebral ischemia. Early reports in humans also suggested benefit in stroke patients treated with HBO. Recent randomized, controlled human studies, however, have not shown benefit, although all were limited by small sample size. Important differences between animal and human studies suggest HBO might be more effective in stroke within the first few hours and at a pressure of 2–3 ATA. Conclusions: The clinical usefulness of HBO in the treatment of cerebral ischemia is not yet certain. Attention to emerging pathophysiologic data should be taken into consideration in design of any future clinical trials of HBO in acute ischemic stroke.

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Reperfusion Injury after Focal Cerebral Ischemia: The Role Inflammation and the The rapeutic Horizon

Cited by 108 publications

References 163 publications

Inhibition of Protein Kinase Cβ Reverses Increased Blood–Brain Barrier Permeability During Hyperglycemic Stroke and Prevents Edema Formation In Vivo

Inhibition of Protein Kinase Cβ Reverses Increased Blood–Brain Barrier Permeability During Hyperglycemic Stroke and Prevents Edema Formation In Vivo

Adhesion Molecules in CNS Disorders: Biomarker and Therapeutic Targets

Hyperbaric Oxygen Therapy of Cerebral Ischemia

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