Stroke-induced opposite and age-dependent changes of vessel-associated markers in co-morbid transgenic mice with Alzheimer-like alterations
| Autor: | Sabine Nissel, Cheryl A. Hawkes, Rebecca Anders, Dominik Michalski, Roxana O. Carare, Jens Grosche, Ingo Bechmann, Wolfgang Härtig |
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| Rok vydání: | 2012 |
| Předmět: |
Genetically modified mouse
CD31 Collagen Type IV Male Pathology medicine.medical_specialty Aging Endothelium Hippocampus Mice Transgenic Biology Basement Membrane Mice Developmental Neuroscience Laminin Alzheimer Disease medicine Animals Basement membrane Neocortex Brain Endothelial Cells Immunohistochemistry Stroke Disease Models Animal medicine.anatomical_structure Neurology biology.protein Female Endothelium Vascular Neuroscience Biomarkers Astrocyte |
| Zdroj: | Experimental neurology. 250 |
| ISSN: | 1090-2430 |
| Popis: | The pathophysiological concept of ischaemic stroke was recently expanded to a more comprehensive perspective, focussing on the vasculature as well as peri- and juxtavascular cells including astrocytes. Increasing evidence also supports a role of the vasculature in Alzheimer's disease (AD), but causal relationships are poorly understood. The purpose of this study was to examine vascular alterations due to cerebral ischaemia in aged wildtype (WT) mice and in the triple-transgenic (3xTg) mouse model of AD. Three- and 12-month-old WT and 3xTg mice underwent permanent middle cerebral artery occlusion. One day after ischaemia onset, expression of collagen IV and laminin as basement membrane constituents, and Solanum tuberosum lectin (STL) as endothelial marker was quantified in the ischaemic neocortex, striatum and hippocampus. Further, CD31- and aquaporin-4-immunoreactivity served for coverage of endothelium and astrocyte endfeet. Ischaemia resulted in strong upregulation of collagen IV and laminin in the neocortex of 3-month-old WT and 3xTg mice, while STL appeared unaffected. Quantification confirmed collagen IV upregulation in the ischaemic neocortex of 3- and 12-month-old WT and 3xTg mice, whereas striatal changes were limited to young WT mice. However, collagen IV expression in the hippocampus appeared nearly unaltered. Qualitative and quantitative data evidenced more severe degeneration of endothelial cells and astrocyte endfeet in 3xTg mice. In conclusion, this study supports the critical impact of the vasculature in the aged and AD brain by showing an age- and genetic background-dependent response of basement membranes to cerebral ischaemia, and a pronounced endothelial and astrocytic degeneration in the AD-like brain. |
| Databáze: | OpenAIRE |
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