Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury
Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer’s disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-03-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00047/full |
| _version_ | 1828844932622712832 |
|---|---|
| author | Zareen Amtul Jun Yang Ting-Yim Lee David F. Cechetto |
| author_facet | Zareen Amtul Jun Yang Ting-Yim Lee David F. Cechetto |
| author_sort | Zareen Amtul |
| collection | DOAJ |
| description | Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer’s disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of β-amyloid (Aβ) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The combination of Aβ and ET1 pathological states leads to an alteration in microvascular anatomy, texture, diameter, density, and protein expression, in addition to disturbed vessel-matrix-connections, inter-compartmental water exchange and basement membrane profile within the lesion epicenter localized in the striatum of Aβ+ET1 brains compared to Aβ and ET1 rats. We conclude that the neural microvascular network, in addition to the neural tissue, is not only sensitive to structural deterioration but also serves as an underlying vascular etiology between ischemia and AD pathologies. Such investigation can provide prospects to appreciate the interrelationships between structure and responses of cerebral microvasculature and to provide a venue for vascular remodeling as a new treatment strategy. |
| first_indexed | 2024-12-12T21:17:03Z |
| format | Article |
| id | doaj.art-0032e8f75269402b833129710167fb72 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T21:17:03Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-0032e8f75269402b833129710167fb722022-12-22T00:11:43ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-03-011110.3389/fnagi.2019.00047432302Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral InjuryZareen Amtul0Jun Yang1Ting-Yim Lee2David F. Cechetto3Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, CanadaRobarts Research Institute, University of Western Ontario, London, ON, CanadaRobarts Research Institute, University of Western Ontario, London, ON, CanadaDepartment of Anatomy and Cell Biology, University of Western Ontario, London, ON, CanadaAberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer’s disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of β-amyloid (Aβ) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The combination of Aβ and ET1 pathological states leads to an alteration in microvascular anatomy, texture, diameter, density, and protein expression, in addition to disturbed vessel-matrix-connections, inter-compartmental water exchange and basement membrane profile within the lesion epicenter localized in the striatum of Aβ+ET1 brains compared to Aβ and ET1 rats. We conclude that the neural microvascular network, in addition to the neural tissue, is not only sensitive to structural deterioration but also serves as an underlying vascular etiology between ischemia and AD pathologies. Such investigation can provide prospects to appreciate the interrelationships between structure and responses of cerebral microvasculature and to provide a venue for vascular remodeling as a new treatment strategy.https://www.frontiersin.org/article/10.3389/fnagi.2019.00047/fullbeta-amyloidischemiamicrovesselsbasement membranevascular anatomy |
| spellingShingle | Zareen Amtul Jun Yang Ting-Yim Lee David F. Cechetto Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury Frontiers in Aging Neuroscience beta-amyloid ischemia microvessels basement membrane vascular anatomy |
| title | Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury |
| title_full | Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury |
| title_fullStr | Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury |
| title_full_unstemmed | Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury |
| title_short | Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury |
| title_sort | pathological changes in microvascular morphology density size and responses following comorbid cerebral injury |
| topic | beta-amyloid ischemia microvessels basement membrane vascular anatomy |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00047/full |
| work_keys_str_mv | AT zareenamtul pathologicalchangesinmicrovascularmorphologydensitysizeandresponsesfollowingcomorbidcerebralinjury AT junyang pathologicalchangesinmicrovascularmorphologydensitysizeandresponsesfollowingcomorbidcerebralinjury AT tingyimlee pathologicalchangesinmicrovascularmorphologydensitysizeandresponsesfollowingcomorbidcerebralinjury AT davidfcechetto pathologicalchangesinmicrovascularmorphologydensitysizeandresponsesfollowingcomorbidcerebralinjury |