Visualization of Leukocytes in the Cerebral Microcirculation After Ischemic Stroke

2.50
Hdl Handle:
http://hdl.handle.net/10755/157605
Type:
Presentation
Title:
Visualization of Leukocytes in the Cerebral Microcirculation After Ischemic Stroke
Abstract:
Visualization of Leukocytes in the Cerebral Microcirculation After Ischemic Stroke
Conference Sponsor:Western Institute of Nursing
Conference Year:2009
Author:Ritter, Leslie S., PhD, RN
P.I. Institution Name:University of Arizona, College of Nursing and Department of Neurology
Title:Associate Professor
Contact Address:Office 302, 1305 N. Martin, PO Box 210203, Tucson, AZ, 85721, USA
Contact Telephone:520-626-3218
Purpose: The purpose of this paper is to discuss our experience using fluorescence microscopy to study the cerebral microcirculation after ischemic stroke in type 2 diabetes. Background: Direct visualization of the microcirculation of various organs can be accomplished by a variety of microscopy methods. These methods allow for the examination of in vivo blood cell-blood vessel interactions during normal and pathophysiologic states. Ischemic stroke is associated with high mortality and disability. In order to more fully understand the reasons for these associations, early work from our laboratory examined how blood leukocytes and their interactions with the cerebral microcirculation might contribute to additional brain injury after ischemic stroke. Using in vivo fluorescence microscopy and a clinically relevant model of ischemic stroke in rodents, we reported that leukocytes adhere to the cerebral microcirculation during the first minutes of reperfusion after stroke, and thus have the potential to contribute to brain damage via toxic mediator release. As an extension of this early work, we were interested in how diabetes, a known risk factor for stroke, might make stroke outcomes worse. We found that in a rodent model of type 2 diabetes, leukocyte CD11b adhesion molecule expression and reactive oxygen species production are increased. We hypothesized that chronic leukocyte activation in type 2 diabetes may result in exaggerated leukocyte adhesion to the cerebral microcirculation during reperfusion after ischemic stroke, and that this inflammatory response may contribute to increased brain injury. Methods: Male, 10-12 week-old Zucker Diabetic Fatty (ZDF, N=4) and Zucker Lean Control (ZLC, N=3) rodents were used. Both groups were anesthetized, intubated, and continuously ventilated. Cannulas were placed in the tail vein and artery for drug administration and blood pressure monitoring, respectively. Arterial blood gases were monitored and maintained within physiologic range. Middle cerebral artery occlusion and reperfusion were then performed using the filament method. Rhodamine, a fluorescent dye that stains leukocytes, was administered. Direct visualization of leukocyte adhesion to the cerebral microcirculation was then accomplished using cranial window and in vivo fluorescence microscopy. Leukocyte adhesion to cerebral venules was videotaped during the first 30 minutes of reperfusion; quantification of leukocyte adhesion was performed on video playback (leuks/100um venule). ANOVA was used to compare leukocyte adhesion between diabetic and non-diabetic groups during the reperfusion period. Results: During early reperfusion following ischemic stroke, leukocyte adhesion to the cerebral microcirculation was significantly greater in the diabetic vs. non-diabetic group (ZDF=12.3 +/- 1.1 leuks/100um venule vs. ZLC=6.2 +/- 0.9 leuks/100um venule; P<0.05). Conclusions and Implications: In a rodent model of type 2 diabetes subjected to ischemic stroke and reperfusion, early and significant leukocyte adhesion to the cerebral microcirculation occurs. It is possible that exaggerated leukocyte adhesion and the subsequent damage leukocytes may cause to the vasculature and surrounding brain tissue may be one explanation for the worse outcomes observed in diabetes and stroke. Furthermore, the methods described herein may be useful in developing potential therapies for these disorders and have great potential for use in nursing research examining vascular disease in a variety of clinical disease processes.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleVisualization of Leukocytes in the Cerebral Microcirculation After Ischemic Strokeen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157605-
dc.description.abstract<table><tr><td colspan="2" class="item-title">Visualization of Leukocytes in the Cerebral Microcirculation After Ischemic Stroke</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2009</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Ritter, Leslie S., PhD, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">University of Arizona, College of Nursing and Department of Neurology</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Associate Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">Office 302, 1305 N. Martin, PO Box 210203, Tucson, AZ, 85721, USA</td></tr><tr class="item-phone"><td class="label">Contact Telephone:</td><td class="value">520-626-3218</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">lritter@nursing.arizona.edu</td></tr><tr><td colspan="2" class="item-abstract">Purpose: The purpose of this paper is to discuss our experience using fluorescence microscopy to study the cerebral microcirculation after ischemic stroke in type 2 diabetes. Background: Direct visualization of the microcirculation of various organs can be accomplished by a variety of microscopy methods. These methods allow for the examination of in vivo blood cell-blood vessel interactions during normal and pathophysiologic states. Ischemic stroke is associated with high mortality and disability. In order to more fully understand the reasons for these associations, early work from our laboratory examined how blood leukocytes and their interactions with the cerebral microcirculation might contribute to additional brain injury after ischemic stroke. Using in vivo fluorescence microscopy and a clinically relevant model of ischemic stroke in rodents, we reported that leukocytes adhere to the cerebral microcirculation during the first minutes of reperfusion after stroke, and thus have the potential to contribute to brain damage via toxic mediator release. As an extension of this early work, we were interested in how diabetes, a known risk factor for stroke, might make stroke outcomes worse. We found that in a rodent model of type 2 diabetes, leukocyte CD11b adhesion molecule expression and reactive oxygen species production are increased. We hypothesized that chronic leukocyte activation in type 2 diabetes may result in exaggerated leukocyte adhesion to the cerebral microcirculation during reperfusion after ischemic stroke, and that this inflammatory response may contribute to increased brain injury. Methods: Male, 10-12 week-old Zucker Diabetic Fatty (ZDF, N=4) and Zucker Lean Control (ZLC, N=3) rodents were used. Both groups were anesthetized, intubated, and continuously ventilated. Cannulas were placed in the tail vein and artery for drug administration and blood pressure monitoring, respectively. Arterial blood gases were monitored and maintained within physiologic range. Middle cerebral artery occlusion and reperfusion were then performed using the filament method. Rhodamine, a fluorescent dye that stains leukocytes, was administered. Direct visualization of leukocyte adhesion to the cerebral microcirculation was then accomplished using cranial window and in vivo fluorescence microscopy. Leukocyte adhesion to cerebral venules was videotaped during the first 30 minutes of reperfusion; quantification of leukocyte adhesion was performed on video playback (leuks/100um venule). ANOVA was used to compare leukocyte adhesion between diabetic and non-diabetic groups during the reperfusion period. Results: During early reperfusion following ischemic stroke, leukocyte adhesion to the cerebral microcirculation was significantly greater in the diabetic vs. non-diabetic group (ZDF=12.3 +/- 1.1 leuks/100um venule vs. ZLC=6.2 +/- 0.9 leuks/100um venule; P&lt;0.05). Conclusions and Implications: In a rodent model of type 2 diabetes subjected to ischemic stroke and reperfusion, early and significant leukocyte adhesion to the cerebral microcirculation occurs. It is possible that exaggerated leukocyte adhesion and the subsequent damage leukocytes may cause to the vasculature and surrounding brain tissue may be one explanation for the worse outcomes observed in diabetes and stroke. Furthermore, the methods described herein may be useful in developing potential therapies for these disorders and have great potential for use in nursing research examining vascular disease in a variety of clinical disease processes.</td></tr></table>en_GB
dc.date.available2011-10-26T20:01:45Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T20:01:45Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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