Splenectomy Does Not Improve Long-Term Outcome After Stroke Jan. 2017
Abstract WP95: Splenectomy Protects Aged Mice From Cerebral Injury in the Experimental Stroke Model
Abstract
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
