The aging ovary impairs acute stroke outcomes
Abstract In experimental stroke, ovariectomized (OVX) adult rats have larger infarct volumes and greater sensory-motor impairment as compared to ovary-intact females and is usually interpreted to indicate that ovarian hormones are neuroprotective for stroke. Previous work from our lab shows that mid...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02839-1 |
| _version_ | 1797784521050947584 |
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| author | Taylor E. Branyan Jocelyn Aleksa Esteban Lepe Kelby Kosel Farida Sohrabji |
| author_facet | Taylor E. Branyan Jocelyn Aleksa Esteban Lepe Kelby Kosel Farida Sohrabji |
| author_sort | Taylor E. Branyan |
| collection | DOAJ |
| description | Abstract In experimental stroke, ovariectomized (OVX) adult rats have larger infarct volumes and greater sensory-motor impairment as compared to ovary-intact females and is usually interpreted to indicate that ovarian hormones are neuroprotective for stroke. Previous work from our lab shows that middle-aged, acyclic reproductively senescent (RS) females have worse stroke outcomes as compared to adult (normally cycling) females. We hypothesized that if loss of ovarian estrogen is the critical determinant of stroke outcomes, then ovary-intact middle-aged acyclic females, who have reduced levels of estradiol, should have similar stroke outcomes as age-matched OVX. Instead, the data demonstrated that OVX RS animals showed better sensory-motor function after stroke and reduced infarct volume as compared to ovary-intact females. Inflammatory cytokines were decreased in the aging ovary after stroke as compared to non-stroke shams, which led to the hypothesis that immune cells may be extravasated from the ovaries post-stroke. Flow cytometry indicated reduced overall T cell populations in the aging ovary after middle cerebral artery occlusion (MCAo), with a paradoxical increase in regulatory T cells (Tregs) and M2-like macrophages. Moreover, in the brain, OVX RS animals showed increased Tregs, increased M2-like macrophages, and increased MHC II + cells as compared to intact RS animals, which have all been shown to be correlated with better prognosis after stroke. Depletion of ovary-resident immune cells after stroke suggests that there may be an exaggerated response to ischemia and possible increased burden of the inflammatory response via extravasation of these cells into circulation. Increased anti-inflammatory cells in the brain of OVX RS animals further supports this hypothesis. These data suggest that stroke severity in aging females may be exacerbated by the aging ovary and underscore the need to assess immunological changes in this organ after stroke. |
| first_indexed | 2024-03-13T00:41:05Z |
| format | Article |
| id | doaj.art-dac9fc1b8dcb47908f90395f9ed034ee |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-13T00:41:05Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-dac9fc1b8dcb47908f90395f9ed034ee2023-07-09T11:19:58ZengBMCJournal of Neuroinflammation1742-20942023-07-0120111810.1186/s12974-023-02839-1The aging ovary impairs acute stroke outcomesTaylor E. Branyan0Jocelyn Aleksa1Esteban Lepe2Kelby Kosel3Farida Sohrabji4Department of Neuroscience and Experimental Therapeutics, Women’s Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of MedicineDepartment of Neuroscience and Experimental Therapeutics, Women’s Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of MedicineDepartment of Neuroscience and Experimental Therapeutics, Women’s Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of MedicineDepartment of Neuroscience and Experimental Therapeutics, Women’s Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of MedicineDepartment of Neuroscience and Experimental Therapeutics, Women’s Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of MedicineAbstract In experimental stroke, ovariectomized (OVX) adult rats have larger infarct volumes and greater sensory-motor impairment as compared to ovary-intact females and is usually interpreted to indicate that ovarian hormones are neuroprotective for stroke. Previous work from our lab shows that middle-aged, acyclic reproductively senescent (RS) females have worse stroke outcomes as compared to adult (normally cycling) females. We hypothesized that if loss of ovarian estrogen is the critical determinant of stroke outcomes, then ovary-intact middle-aged acyclic females, who have reduced levels of estradiol, should have similar stroke outcomes as age-matched OVX. Instead, the data demonstrated that OVX RS animals showed better sensory-motor function after stroke and reduced infarct volume as compared to ovary-intact females. Inflammatory cytokines were decreased in the aging ovary after stroke as compared to non-stroke shams, which led to the hypothesis that immune cells may be extravasated from the ovaries post-stroke. Flow cytometry indicated reduced overall T cell populations in the aging ovary after middle cerebral artery occlusion (MCAo), with a paradoxical increase in regulatory T cells (Tregs) and M2-like macrophages. Moreover, in the brain, OVX RS animals showed increased Tregs, increased M2-like macrophages, and increased MHC II + cells as compared to intact RS animals, which have all been shown to be correlated with better prognosis after stroke. Depletion of ovary-resident immune cells after stroke suggests that there may be an exaggerated response to ischemia and possible increased burden of the inflammatory response via extravasation of these cells into circulation. Increased anti-inflammatory cells in the brain of OVX RS animals further supports this hypothesis. These data suggest that stroke severity in aging females may be exacerbated by the aging ovary and underscore the need to assess immunological changes in this organ after stroke.https://doi.org/10.1186/s12974-023-02839-1Reproductive senescenceMCAoSensorimotor impairmentOvarian cytokinesT cellsMacrophages |
| spellingShingle | Taylor E. Branyan Jocelyn Aleksa Esteban Lepe Kelby Kosel Farida Sohrabji The aging ovary impairs acute stroke outcomes Journal of Neuroinflammation Reproductive senescence MCAo Sensorimotor impairment Ovarian cytokines T cells Macrophages |
| title | The aging ovary impairs acute stroke outcomes |
| title_full | The aging ovary impairs acute stroke outcomes |
| title_fullStr | The aging ovary impairs acute stroke outcomes |
| title_full_unstemmed | The aging ovary impairs acute stroke outcomes |
| title_short | The aging ovary impairs acute stroke outcomes |
| title_sort | aging ovary impairs acute stroke outcomes |
| topic | Reproductive senescence MCAo Sensorimotor impairment Ovarian cytokines T cells Macrophages |
| url | https://doi.org/10.1186/s12974-023-02839-1 |
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