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The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse
Published on: July 25, 2011
Leukocyte-endothelium interactions during permanent focal cerebral ischemia in mice
Hiroharu Kataoka1, Seong-Woong Kim, Nikolaus Plesnila
1Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany.
Insights
Leukocyte infiltration increases in the brain after permanent stroke, even without reperfusion. This leukocyte-endothelial interaction in cerebral vessels may contribute to stroke-induced brain damage.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- The role of leukocyte infiltration in brain damage following permanent focal cerebral ischemia is not fully understood.
- Molecular mechanisms driving leukocyte accumulation in the brain post-stroke require further investigation.
Purpose of the Study:
- To develop a mouse model for in vivo visualization of leukocytes in the cerebral microcirculation.
- To investigate leukocyte-endothelial interactions (LEI) after permanent middle cerebral artery occlusion (MCAO).
Main Methods:
- Utilized intravital fluorescent microscopy in a mouse model.
- Induced permanent focal cerebral ischemia via middle cerebral artery occlusion (MCAO).
- Quantified rolling and adherent leukocytes in pial venules and arterioles.
Main Results:
- Physiologic LEI was observed in sham-operated mice.
- Permanent MCAO significantly increased LEI in pial venules.
- Rolling and adherent leukocytes were also detected in arterioles of ischemic mice.
Conclusions:
- Leukocytes accumulate in the brain following permanent focal cerebral ischemia, independent of reperfusion.
- Increased leukocyte-endothelial interaction in cerebral microcirculation may contribute to brain damage after stroke.
Abstract:
The contribution of leukocyte infiltration to brain damage after permanent focal cerebral ischemia and the underlying molecular mechanisms are still unclear. Therefore, the aim of this study was to establish a mouse model for the visualization of leukocytes in the cerebral microcirculation in vivo and to investigate leukocyte-endothelial interaction (LEI) after permanent middle cerebral artery occlusion (MCAO). Sham-operated 129/Sv mice showed physiologic LEI in pial venules as observed by intravital fluorescent microscopy. Permanent focal cerebral ischemia induced a significant increase of LEI predominantly in pial venules. The number of rolling and adherent leukocytes reached 36.5 +/- 13.2/100 microm x min and 22.5 +/- 7.9/100 microm x min, respectively at 120 minutes after MCAO (P = 0.016 vs. control). Of note, rolling and adherent leukocytes were also observed in arterioles of ischemic animals (7.3 +/- 3.0/100 microm x min rolling and 3.0 +/- 3.6/100 microm x min adherent). Capillary density was not different between groups. These results demonstrate that leukocytes accumulate in the brain not only after transient but also after permanent focal cerebral ischemia and may therefore contribute to brain damage after stroke without reperfusion.
