Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats.

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Background and Purpose-Neutrophil (PMN) recruitment mediated by increased expression of intercellular adhesion molecule-1 expression (ICAM-1, CD54) in the cerebral microvasculature contributes to the pathogenesis of tissue injury in stroke. However, studies using blocking antibodies against the common ␤ 2 -integrin subunit on the PMN, the counterligand for ICAM-1 (CD18), have demonstrated equivocal efficacy. The current study tested the hypothesis that mice deficient in CD18 would be protected in the setting of reperfused but not nonreperfused stroke. Methods-Two groups of mice were studied, those whose PMNs could express CD18 (CD18 ϩ/ϩ) and those mice hypomorphic for the CD-18 gene (CD18 Ϫ/Ϫ). PMNs obtained from CD18 Ϫ/Ϫ or CD18 ϩ/ϩ mice were fluorescently labeled and tested for binding to murine brain endothelial monolayers. Using a murine model of focal cerebral ischemia in which an occluding suture placed in the middle cerebral artery (MCA) is removed after 45 minutes (transient ischemia, reperfused stroke) or left in place (permanent ischemia, nonreperfused stroke), cerebral infarct volumes (% ipsilateral hemisphere by TTC staining), cerebral blood flow (CBF, % contralateral hemisphere by laser-Doppler flowmetry), and survival (%) were examined 24 hours after the initial ischemic event. Adoptive transfer studies used

Section: Discussionmentioning

confidence: 84%

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confidence: 99%

CD18-Mediated Neutrophil Recruitment Contributes to the Pathogenesis of Reperfused but Not Nonreperfused Stroke

Prestigiacomo

Kim

Connolly

et al. 1999

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122

“…5,6 However, administration of this antibody also led to partial peripheral white blood cell depletion. Treatment with an antibody to the CD18 subunit has yielded controversial results; in a feline model, the antibody did not alter cerebral blood flow or infarct volume, 7 whereas in a primate model, it improved microvascular patency after cerebral ischemia/ reperfusion. 8 Antibody-antigen interactions can lead to complex responses, including triggering of signal transduction events and incomplete inactivation of functional binding sites on the target molecule.…”

Section: See Editorial Comment Page 139mentioning

confidence: 99%

Mice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury

Soriano

Coxon

Wang

et al. 1999

203

142

Background and Purpose-Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte ␤2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1. Methods-Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1-deficient (nϭ12) and wild-type (nϭ11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils. Results-Compared with the wild-type cohort, Mac-1-deficient mice had a 26% reduction in infarction volume (PϽ0.05).This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups. Conclusions-Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1-deficient mice. (Stroke. 1999;30:134-139.)

“…13-u ' 18 After injury volume was estimated, the slices of brain were placed in 10% buffered formalin for 1 to 2 days. Ipsilateral and contralateral temporal and parietal lobes of the middle four slices were subsequently sectioned into three cortical gray matter regions (inferior temporal, lateral temporal-parietal, and superior parietal) for regional CBF determinations.…”

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confidence: 99%

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

Nishikawa

Kirsch

Koehler

et al. 1994

Self Cite

Background and PurposeWe tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury.Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of reperfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5).Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetrazolium-determined injury volume of ipsilateral cerebral hemi-