Aging exacerbates development of cerebral microbleeds in a mouse model
Abstract Background Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationshi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1092-x |
| _version_ | 1818408296272363520 |
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| author | Rachita K. Sumbria Mher Mahoney Grigoryan Vitaly Vasilevko Annlia Paganini-Hill Kelley Kilday Ronald Kim David H. Cribbs Mark J. Fisher |
| author_facet | Rachita K. Sumbria Mher Mahoney Grigoryan Vitaly Vasilevko Annlia Paganini-Hill Kelley Kilday Ronald Kim David H. Cribbs Mark J. Fisher |
| author_sort | Rachita K. Sumbria |
| collection | DOAJ |
| description | Abstract Background Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age. Methods We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry. Results Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice. Conclusions Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation. |
| first_indexed | 2024-12-14T09:41:28Z |
| format | Article |
| id | doaj.art-517c9a145ed4476fafe8379ce8c3fbec |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-14T09:41:28Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-517c9a145ed4476fafe8379ce8c3fbec2022-12-21T23:07:46ZengBMCJournal of Neuroinflammation1742-20942018-03-011511710.1186/s12974-018-1092-xAging exacerbates development of cerebral microbleeds in a mouse modelRachita K. Sumbria0Mher Mahoney Grigoryan1Vitaly Vasilevko2Annlia Paganini-Hill3Kelley Kilday4Ronald Kim5David H. Cribbs6Mark J. Fisher7Department of Biopharmaceutical Sciences, School of Pharmacy, Keck Graduate InstituteDepartment of Neurology, University of CaliforniaInstitute for Memory Impairments and Neurological Disorders, University of CaliforniaDepartment of Neurology, University of CaliforniaInstitute for Memory Impairments and Neurological Disorders, University of CaliforniaDepartment of Pathology and Laboratory Medicine, University of CaliforniaInstitute for Memory Impairments and Neurological Disorders, University of CaliforniaDepartment of Neurology, University of CaliforniaAbstract Background Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age. Methods We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry. Results Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice. Conclusions Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation.http://link.springer.com/article/10.1186/s12974-018-1092-xAnimal modelsCerebral microhemorrhageCerebral microbleedsInflammationHemosiderinAging |
| spellingShingle | Rachita K. Sumbria Mher Mahoney Grigoryan Vitaly Vasilevko Annlia Paganini-Hill Kelley Kilday Ronald Kim David H. Cribbs Mark J. Fisher Aging exacerbates development of cerebral microbleeds in a mouse model Journal of Neuroinflammation Animal models Cerebral microhemorrhage Cerebral microbleeds Inflammation Hemosiderin Aging |
| title | Aging exacerbates development of cerebral microbleeds in a mouse model |
| title_full | Aging exacerbates development of cerebral microbleeds in a mouse model |
| title_fullStr | Aging exacerbates development of cerebral microbleeds in a mouse model |
| title_full_unstemmed | Aging exacerbates development of cerebral microbleeds in a mouse model |
| title_short | Aging exacerbates development of cerebral microbleeds in a mouse model |
| title_sort | aging exacerbates development of cerebral microbleeds in a mouse model |
| topic | Animal models Cerebral microhemorrhage Cerebral microbleeds Inflammation Hemosiderin Aging |
| url | http://link.springer.com/article/10.1186/s12974-018-1092-x |
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