title: Differential effects of aging and sex on stroke induced inflammation across the lifespan.
abstract: Aging and biological sex are critical determinants of stroke outcome. Post-ischemic inflammatory response strongly contributes to the extent of ischemic brain injury, but how this response changes with age and sex is unknown. We subjected young (5-6 months), middle aged (14-15 months) and aged (20-22 months), C57BL/6 male and female mice to transient middle cerebral artery occlusion (MCAO) and found that a significant age by sex interaction influenced histological stroke outcomes. Acute functional outcomes were worse with aging. Neutrophils, inflammatory macrophages, macrophages, dendritic cells (DCs) and microglia significantly increased in the brain post MCAO. Cycling females had higher Gr1(-) non-inflammatory macrophages and lower T cells in the brain after stroke and these correlated with serum estradiol levels. Estrogen loss in acyclic aged female mice exacerbated stroke induced splenic contraction. Advanced age increased T cells, DCs and microglia at the site of injury, which may be responsible for the exacerbated behavioral deficits in the aged. We conclude that aging and sex have differential effects on the post stroke inflammatory milieu. Putative immunomodulatory therapies need to account for this heterogeneity.
authors.affiliation: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA; Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Bharti
authors.initials: B
authors.lastname: Manwani
authors.forename: Fudong
authors.initials: F
authors.lastname: Liu
authors.forename: Victoria
authors.initials: V
authors.lastname: Scranton
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hammond
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Sansing
authors.forename: Louise D
authors.initials: LD
authors.lastname: McCullough
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012727:Sex Characteristics; D020521:Stroke / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
keywords: Age; Estrogen; Flow cytometry; Immunity; Ischemia; Sex