Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration
Chronic neurodegenerative diseases are characterized by substantial inflammation with putative impairment of the brain vasculature also commonly observed. To address effects of chronic neurodegeneration on the regional vasculature under experimentally controlled circumstances, the glutamate receptor...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003632 |
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| author | Maj Schneider Thomsen Serhii Kostrikov Lisa Greve Routhe Kasper Bendix Johnsen Steinunn Sara Helgudóttir Johann Mar Gudbergsson Thomas Lars Andresen Torben Moos |
| author_facet | Maj Schneider Thomsen Serhii Kostrikov Lisa Greve Routhe Kasper Bendix Johnsen Steinunn Sara Helgudóttir Johann Mar Gudbergsson Thomas Lars Andresen Torben Moos |
| author_sort | Maj Schneider Thomsen |
| collection | DOAJ |
| description | Chronic neurodegenerative diseases are characterized by substantial inflammation with putative impairment of the brain vasculature also commonly observed. To address effects of chronic neurodegeneration on the regional vasculature under experimentally controlled circumstances, the glutamate receptor agonist ibotenic acid was injected into striatum of adult rats, which causes excitotoxicity in the substantia nigra pars reticulata (SNpr) due to imbalance between inhibitory inputs from the striatum and excitatory signals from the subthalamic nucleus. Brains were examined at 28 days (short-term neurodegeneration) and 91 days (long-term neurodegeneration) and analyzed for vascular remodeling taking both 2D and 3D approaches, the latter involving confocal microscopy of optically cleared samples combined with machine learning-based image analysis. Crysectioned and microdissected samples were analyzed for protein and gene expression respectively. The resulting neurodegeneration was accompanied by regional tissue loss and inflammation. The 3D analysis of the degenerating SNpr revealed substantial changes of the vasculature with higher density, increased diameter, and number of tortuous vessels already after 28 days, evidently continuing at 91 days. Interestingly, the vascular remodeling changes occurred without changes in the expression of endothelial tight junction proteins, vascular basement membrane proteins, or markers of angiogenesis. We propose that remodeling of the vasculature in neurodegeneration occurs due to regional tissue atrophy, which leaves the vasculature operating but prone to additional pathologies. |
| format | Article |
| id | doaj-art-607b7884e61944daa619ca932725c488 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-607b7884e61944daa619ca932725c4882025-01-07T04:17:08ZengElsevierNeurobiology of Disease1095-953X2025-01-01204106761Remodeling of the brain angioarchitecture in experimental chronic neurodegenerationMaj Schneider Thomsen0Serhii Kostrikov1Lisa Greve Routhe2Kasper Bendix Johnsen3Steinunn Sara Helgudóttir4Johann Mar Gudbergsson5Thomas Lars Andresen6Torben Moos7Neurobiology research and drug delivery, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkDepartment of Health Technology, Technical University of Denmark, Kgs. Lyngby, DenmarkNeurobiology research and drug delivery, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkDepartment of Health Technology, Technical University of Denmark, Kgs. Lyngby, DenmarkNeurobiology research and drug delivery, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkNeurobiology research and drug delivery, Department of Health Science and Technology, Aalborg University, Aalborg, DenmarkDepartment of Health Technology, Technical University of Denmark, Kgs. Lyngby, DenmarkNeurobiology research and drug delivery, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; Corresponding author at: Aalborg University, Neurobiology research and drug delivery, Department of Health Science and Technology, Selma Lagerlöfs Vej 249, DK-9220 Aalborg, Denmark.Chronic neurodegenerative diseases are characterized by substantial inflammation with putative impairment of the brain vasculature also commonly observed. To address effects of chronic neurodegeneration on the regional vasculature under experimentally controlled circumstances, the glutamate receptor agonist ibotenic acid was injected into striatum of adult rats, which causes excitotoxicity in the substantia nigra pars reticulata (SNpr) due to imbalance between inhibitory inputs from the striatum and excitatory signals from the subthalamic nucleus. Brains were examined at 28 days (short-term neurodegeneration) and 91 days (long-term neurodegeneration) and analyzed for vascular remodeling taking both 2D and 3D approaches, the latter involving confocal microscopy of optically cleared samples combined with machine learning-based image analysis. Crysectioned and microdissected samples were analyzed for protein and gene expression respectively. The resulting neurodegeneration was accompanied by regional tissue loss and inflammation. The 3D analysis of the degenerating SNpr revealed substantial changes of the vasculature with higher density, increased diameter, and number of tortuous vessels already after 28 days, evidently continuing at 91 days. Interestingly, the vascular remodeling changes occurred without changes in the expression of endothelial tight junction proteins, vascular basement membrane proteins, or markers of angiogenesis. We propose that remodeling of the vasculature in neurodegeneration occurs due to regional tissue atrophy, which leaves the vasculature operating but prone to additional pathologies.http://www.sciencedirect.com/science/article/pii/S0969996124003632AngioarchitectureNeurodegenerationCerebrovascular pathologyBrain vasculatureBasement membraneIn vivo models |
| spellingShingle | Maj Schneider Thomsen Serhii Kostrikov Lisa Greve Routhe Kasper Bendix Johnsen Steinunn Sara Helgudóttir Johann Mar Gudbergsson Thomas Lars Andresen Torben Moos Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration Neurobiology of Disease Angioarchitecture Neurodegeneration Cerebrovascular pathology Brain vasculature Basement membrane In vivo models |
| title | Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| title_full | Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| title_fullStr | Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| title_full_unstemmed | Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| title_short | Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| title_sort | remodeling of the brain angioarchitecture in experimental chronic neurodegeneration |
| topic | Angioarchitecture Neurodegeneration Cerebrovascular pathology Brain vasculature Basement membrane In vivo models |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003632 |
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