Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Ishikawa, Mami; Sekizuka, Eliichi; Sato, Shuzo; Yamaguchi, Noriyuki; Inamasu, Joji; Bertalanffy, Helmut; Kawase, Takeshi

doi:10.1161/01.str.30.8.1679

Cited by 76 publications

(53 citation statements)

References 50 publications

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“…Leukocyte-endothelial cell interactions have been previously described in porcine (Gidday et al, 1997), gerbil (Uhl et al, 2000), rat (Dirnagl et al, 1994), and murine (Ishikawa et al, 2003) models of global I/R, and after focal I/R in the rat (Ishikawa et al, 1999;Ritter et al, 2000). The present study represents the first attempt to systematically evaluate the effects of focal I/R on the…”

Section: Time Course Of Platelet and Leukocyte Adhesion In Focal Ischmentioning

confidence: 70%

Platelet–Leukocyte–Endothelial Cell Interactions after Middle Cerebral Artery Occlusion and Reperfusion

Ishikawa

Cooper

Arumugam

et al. 2004

J Cereb Blood Flow Metab

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140

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Summary:The adhesion of both leukocytes and platelets to microvascular endothelial cells has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds. The objectives of this study were to (1) assess the platelet-leukocyte-endothelial cell interactions induced in the cerebral microvasculature by middle cerebral artery occlusion (MCAO)/reperfusion, and (2) define the molecular determinants of the prothrombogenic and inflammatory responses in this model of focal I/R. MCAO was induced for 1 hour in wild-type (WT) mice, WT mice treated with a monoclonal antibody (mAb) to either P-selectin or GPIIb/IIIa, and in P-selectin) chimeras. Isolated platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) were administered intravenously and observed with intravital fluorescence microscopy. Leukocytes were observed after intravenous injection of rhodamine 6G. One hour of MCAO followed by 1 hour of reperfusion resulted in the rolling and adhesion of leukocytes in venules, and after 4 hours of reperfusion, the adhesion of both leukocytes and platelets was detected. Although both the P-selectin and GPIIb/IIIa mAbs significantly reduced the adhesion of leukocytes and platelets at 4 hours of reperfusion, the antiadhesive effects of the P-selectin mAb were much greater. The leukocyte and platelet adhesion responses were significantly attenuated in both P-sel −/− →WT and WT→P-sel −/− bone marrow chimeras, compared with WT→WT chimeras. Neutropenia, induced by antineutrophil serum treatment, also reduced the recruitment of leukocytes and platelets after cerebral I/R. These findings implicate a major role for both platelet-associated and endothelial cellassociated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R.

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Section: Time Course Of Platelet and Leukocyte Adhesion In Focal Ischmentioning

confidence: 70%

Platelet–Leukocyte–Endothelial Cell Interactions after Middle Cerebral Artery Occlusion and Reperfusion

Ishikawa

Cooper

Arumugam

et al. 2004

J Cereb Blood Flow Metab

Self Cite

140

123

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“…33 Other ischemia studies have confirmed that the preponderant locus of leukocyte adherence is to venular endothelium, which occurs during the first 3 hours of reperfusion and is suppressed by moderate hypothermia. 31,34,35 By contrast, leukocyte adhesion within arterioles is less prominent. 33,34 Transient MCAO with reperfusion appears to result in earlier neutrophil accumulation than permanent MCAO.…”

Section: Discussionmentioning

confidence: 99%

“…31,34,35 By contrast, leukocyte adhesion within arterioles is less prominent. 33,34 Transient MCAO with reperfusion appears to result in earlier neutrophil accumulation than permanent MCAO. 36,37 When complete cerebral ischemia is of brief duration, accumulated leukocytes are dislodged from cerebral capillaries, 38 while under conditions of persistently diminished cerebral perfusion, leukocytes may accumulate for several hours.…”

Section: Discussionmentioning

confidence: 99%

Albumin Therapy of Transient Focal Cerebral Ischemia

Belayev

Pinard

Nallet

et al. 2002

Stroke

151

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Background and Purpose-To study whether intravascular or hemodynamic factors contribute to the marked neuroprotective effect of albumin therapy in focal cerebral ischemia, 2 complementary methods were applied: laser-scanning confocal microscopy (LSCM) and laser-Doppler perfusion imaging (LDPI). Methods-In the LSCM study, Sprague-Dawley rats were anesthetized with halothane/nitrous oxide, and a cranial window was placed over the dorsolateral frontoparietal cortex. Rats received 2-hour middle cerebral artery occlusion (MCAO) by an intraluminal suture and were treated with human albumin (1.25 g/kg; nϭ4) or saline (nϭ3) after 30 minutes of recirculation. Video images of cortical vessels were continually acquired and were digitized offline to measure diameters and fluorescent erythrocyte velocities. In the LDPI study, cortical perfusion was measured in anesthetized SpragueDawley rats that received 2-hour MCAO and were treated with albumin (2.5 g/kg; nϭ6) or saline (nϭ5) at 30 minutes after recirculation. Results-In the LSCM study, MCAO was associated with arteriolar dilation and slowing of capillary and venular erythrocyte perfusion. During the first 15 to 30 minutes of postischemic recirculation, prominent foci of vascular stagnation developed within cortical venules, associated with thrombuslike foci and adherent corpuscular structures consistent in size with neutrophils. Saline administration failed to affect these phenomena, while albumin therapy was followed by significant increases in arteriolar diameter (Ϸ12%; Pϭ0.007) and by a prompt improvement of venular and capillary erythrocyte perfusion and a partial disappearance of adherent thrombotic material. Albumin therapy increased erythrocyte flow velocity in both capillaries (288Ϯ73% versus 76Ϯ18% in the saline group; Pϭ0.023) and venules (2.7-fold [Pϭ0.001] versus 1.0-fold in the saline group [PϭNS]). In the LDPI study, cortical perfusion declined during MCAO and rose initially with recirculation (to Ϸ135% of baseline) in both groups. Mean cortical perfusion improved slightly (Ϸ14%; PϭNS) in albumin-treated animals. Conclusions-These results reveal a beneficial effect of albumin therapy in reversing stagnation, thrombosis, and corpuscular adherence within cortical venules in the reperfusion phase after focal ischemia and support its utility in the treatment of acute ischemic stroke.

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“…Leukocyte recruitment has been reported in models of both global [1][2][3][4] and focal [5][6][7] cerebral ischemia/reperfusion (I/R). Manipulation of several adhesion molecules that mediate leukocyte-endothelial interactions, in particular, intercellular adhesion molecule-1 and P-selectin, has revealed a role for I/R-induced leukocyte recruitment in the pathogenesis of the resultant organ injury found in the brain.…”

mentioning

confidence: 99%

CD40/CD40 Ligand Signaling in Mouse Cerebral Microvasculature After Focal Ischemia/Reperfusion

et al. 2005

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Background-CD40/CD40 ligand (CD40L) signaling contributes to proinflammatory and prothrombogenic responses in the vasculature. CD40/CD40L expression is elevated in patients after a transient ischemic attack or stroke. The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion. Methods and Results-Intravital fluorescence microscopy was used to visualize the cerebral microcirculation of wild-type (WT), CD40-deficient, and CD40L-deficient mice subjected to 1-hour MCAO and 4-hour reperfusion. The adhesion of platelets and of leukocytes and vascular permeability were measured in postcapillary venules after 4-hour and 1-hour reperfusions, respectively. Cerebral infarct volume was analyzed 24 hours after reperfusion. Platelet and leukocyte adhesion was elevated and blood/brain barrier function was compromised by MCAO in WT mice. Blood cell recruitment and increased permeability were blunted in both CD40-deficient and CD40L-deficient mice. Infarct volume was also reduced in CD40-and CD40L-deficient mice compared with WT mice. Conclusions-Our findings indicate that CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by MCAO and reperfusion. The CD40/CD40L dyad may play a significant pathogenic role in the acute phase of ischemic stroke.

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Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Cited by 76 publications

References 50 publications

Platelet–Leukocyte–Endothelial Cell Interactions after Middle Cerebral Artery Occlusion and Reperfusion

Platelet–Leukocyte–Endothelial Cell Interactions after Middle Cerebral Artery Occlusion and Reperfusion

Albumin Therapy of Transient Focal Cerebral Ischemia

CD40/CD40 Ligand Signaling in Mouse Cerebral Microvasculature After Focal Ischemia/Reperfusion

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