Abstract WMP75: Age- and Sex-Specific Development of Cerebral Microbleeds in a Mouse Model

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Cerebral microbleeds (CMB), a common MRI finding that may predict intracerebral hemorrhage, are based on a pathological substrate of cerebral microhemorrhages (CMH). Recent clinical and laboratory studies have demonstrated the importance of systemic inflammation in the development of CMB. The effects of age and sex on CMB development have not been well-defined. In the current study, we hypothesized that there are age and sex differences in the pathogenesis of inflammation-induced CMB in mice. We studied young (3 months, n=39) and old (17 months, n=25) male and female C57BL/6 mice injected with LPS (1mg/kg, i.p.) or saline at 0, 6, and 24h. 7 days after first LPS injection, cardiac perfusion was performed, mice were sacrificed, and brains were harvested. CMH grossly visible on the brain surface were examined and 40 μm brain sections were prepared and stained with hematoxylin and eosin (H&E) to estimate the acute/fresh parenchymal CMH number, size and total area in young versus old mice. No surface CMH and negligible H&E-positive parenchymal CMH were observed in young and old saline controls. LPS treatment significantly (p<0.001) increased the development of surface CMH in aged male mice (mean±SEM=17±6 surface microhemorrhages/brain) compared to young male mice (2.8±1.5 surface microhemorrhages/brain). Negligible H&E-positive CMH were observed in LPS-treated young mice. Aging increased the number (1.3±0.7 vs 0.09±0.05 CMH/section; p<0.05), size (4510±1431 vs 471±188 μm2; p<0.001) and area (0.03±0.02 vs 0.0005±0.0003 % total area; p<0.01) of H&E-positive parenchymal CMH in old LPS-treated male mice compared to young LPS-treated male mice. Consistent with previous studies from our lab, H&E-positive CMH were predominantly located in the cerebellum compared to the cortex and sub-cortex. No significant differences were observed in LPS-induced surface or parenchymal CMH development between young and aged female mice. In summary, effects of aging on LPS-induced microbleed development are demonstrable in males. Aging makes the brain more susceptible to inflammation-induced cerebral microbleeds in male mice.

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