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Published on: May 5, 2023
The aging ovary impairs acute stroke outcomes
Taylor E Branyan1,2, Jocelyn Aleksa1, Esteban Lepe1
1Department of Neuroscience and Experimental Therapeutics, Women's Health in Neuroscience Program, Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine, 8447 Riverside Pkwy, Bryan, TX, 77807, USA.
In aging female rats, removing the ovaries improved stroke outcomes, contrary to expectations. This suggests the aging ovary may worsen stroke severity by releasing inflammatory immune cells.
Area of Science:
- Neuroscience
- Immunology
- Reproductive Biology
Background:
- Ovarian hormones are generally considered neuroprotective against stroke in adult females.
- Reproductively senescent (RS) females exhibit worse stroke outcomes than normally cycling females.
- The role of the aging ovary in stroke outcomes, particularly in RS females, remains unclear.
Purpose of the Study:
- To investigate the impact of ovariectomy (OVX) on stroke outcomes in middle-aged, reproductively senescent (RS) female rats.
- To explore the immunological changes in the ovary and brain following stroke in RS rats.
- To determine if the aging ovary exacerbates stroke severity.
Main Methods:
- Middle cerebral artery occlusion (MCAo) model of stroke in adult OVX and ovary-intact RS rats.
- Assessment of sensory-motor function and infarct volume post-stroke.
- Flow cytometry analysis of immune cell populations (T cells, Tregs, M2 macrophages) in the ovary and brain.
Main Results:
- OVX RS rats exhibited significantly better sensory-motor function and reduced infarct volume compared to ovary-intact RS rats.
- The aging ovary showed decreased inflammatory cytokines and altered immune cell profiles (increased Tregs, M2 macrophages) post-stroke.
- OVX RS rats displayed increased Tregs and M2-like macrophages in the brain, correlating with better stroke prognosis.
Conclusions:
- Contrary to the neuroprotective role of ovarian hormones in young females, the aging ovary in RS females appears to exacerbate stroke severity.
- Depletion of ovary-resident immune cells after stroke, with increased anti-inflammatory cells in the brain of OVX rats, suggests a detrimental role of the aging ovary.
- These findings highlight the need to consider immunological changes in the aging ovary after stroke in female rodents.
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