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Updated: Aug 16, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Focal cerebral ischemia induces changes in both MMP-13 and aggrecan around individual neurons
Simon Nagel1, John D Sandy, Uta Meyding-Lamade
1Department of Neurology University of Heidelberg, Medical School, Heidelberg, Germany. simon_nagel@med.uni-heidelberg.de
Introduction:
To test the hypothesis that matrix metalloprotease-13 (MMP-13) and aggrecan may play roles in post-ischemic neuronal pathophysiology, we examined the impact of middle cerebral artery occlusion/reperfusion (MCAO/R) on the abundance of these proteins in different regions of the infarct by immunohistochemistry (IHC) and Western blotting (WB).
Methods:
The effect of MCAO/R on the abundance of MMP-13 and aggrecan was examined in 23 Wistar rats using antibodies against MMP-13 and aggrecan. BrdU was administered the last 2 days of the experiment. The cellular source of the respective antigens was examined with fluorescent double labeling using the neuronal marker NeuN. Sections were also stained for BrdU. The ischemic zone was defined by MRI on T2-weighted images and also on the tissue sections with the help of H and E counterstain. WB was performed for MMP-13.
Results:
MMP-13 protein is highly induced in ischemic brain and is associated with neurons, whereas aggrecan is associated with the perineuronal matrix in non-ischemic brain. After 3 days of cerebral ischemia, the number of MMP-13 positive neurons in the periphery of the ischemic lesion increased compared to the respective area in the non-ischemic brain with a peak on day 7. A stronger staining for aggrecan was observed around MMP-13 positive neurons compared with other neurons. The majority of the MMP-13 positive neurons in normal non-ischemic brain were also NeuN positive. BrdU was incorporated into MMP-13 positive neurons in the periphery of the infarct. WB confirmed this results by detecting MMP-13 bands in ischemic brains and activated MMP-13 up to 14 days after ischemia.
Conclusions:
There is a close spatial association of MMP-13 and aggrecan around individual neurons. Both MMP-13 and aggrecan appear to be involved in perineuronal matrix remodeling suggesting a role in neuronal reorganization after cerebral ischemia.
Insights
Matrix metalloprotease-13 (MMP-13) and aggrecan are upregulated in ischemic brain regions after stroke. These proteins are closely associated with neurons, suggesting a role in brain repair and reorganization following cerebral ischemia.
Area of Science:
- Neuroscience
- Biochemistry
- Pathophysiology
Background:
- Matrix metalloprotease-13 (MMP-13) and aggrecan are investigated for their potential roles in post-ischemic neuronal damage.
- Cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO/R), serves as the experimental model.
Purpose of the Study:
- To test the hypothesis that MMP-13 and aggrecan are involved in post-ischemic neuronal pathophysiology.
- To examine the impact of MCAO/R on the abundance and localization of MMP-13 and aggrecan in the ischemic brain.
Main Methods:
- Immunohistochemistry (IHC) and Western blotting (WB) were used to analyze MMP-13 and aggrecan levels in Wistar rats subjected to MCAO/R.
- BrdU labeling and immunofluorescence with neuronal marker NeuN identified cell proliferation and neuronal association.
- Magnetic Resonance Imaging (MRI) defined the ischemic zone.
Main Results:
- MMP-13 protein was significantly induced in the ischemic brain and localized to neurons.
- Aggrecan was found in the perineuronal matrix, with increased association around MMP-13 positive neurons post-ischemia.
- WB confirmed the presence of MMP-13 in ischemic brains up to 14 days after ischemia.
Conclusions:
- MMP-13 and aggrecan exhibit a close spatial association around individual neurons.
- Both proteins are implicated in perineuronal matrix remodeling, suggesting a role in neuronal reorganization after cerebral ischemia.
