Introduction: Aging is a non-modifiable risk factor for stroke. Although aged animals tend to have smaller infarcts they have worse functional recovery after stroke, suggesting difference in mechanisms between young and aged. Splenectomy reduces infarct in animal models, but how the spleen contributes to brain injury in aged mice has not been as well studied.
Hypothesis: We hypothesized that peripheral inflammation increases over the lifespan. We predicted that the detrimental effects of the spleen would be reversed by splenectomy in aged mice.
Methods: Young and aged male mice were splenectomized (n= 8-9), 2 weeks prior to induction of 1 hour of middle cerebral artery occlusion. Ninety-six hours after reperfusion, behavioral and infarct area was assessed. In a separate cohort, peripheral and central immune cells were quantified by flow cytometry.
Results: After stroke, there was 13.3, 17.7, 25.9 and 5.88% mortality in spleen intact young, splenecyomized young, spleen intact aged and splenctomized aged mice respectively. Splenectomy led to improved behavioral deficits in aged mice as seen by lower neurological deficits scores,(1.63 ± 0.26 Vs 2.57 ± 0.20) and reduction in number of right turns in the corner test. There was significant reduction in infarct size in the splenectomized aged mice (p<0.05) as compared to spleen-intact mice. Splenectomy in aged mice lead to reduction in the frequency of CD3CD44+ T cells. Additionally, there was significant decrease in TNF-α, IL-6, IL-4, IL-12MIP-1b and RANTES levels in the aged splenectomized aged mice as compared to spleen-intact aged mice (p<0.05). In the brain, the frequency of CD45hiCD11b+ cells was reduced in the splenectomized MCAo aged as compared to spleen-intact stroke mice (p<0.05).
Conclusions: Splenectomy reduced the peripheral activation of T cells in the aged mice. Also less peripheral leukocyte infiltration was observed, which mirrored improved functional recovery and reduced infarct damage in splenectomized aged mice. Hence, this study provides new information regarding age specific peripheral immune responses and interaction with the brain after experimental stroke highlighting a need for the incorporation of aged mice in the basic stroke research. Funding: 16POST27490032