Abstract 201: Changes In Inflammatory Response To Ischemic Stroke Across The Life Span

Abstract

Background/Purpose- Inflammation plays a critical role in the response to stroke, and post-ischemic inflammatory responses strongly contribute to the extent of ischemic brain injury. Although much is known about the post stroke inflammatory cascade in brain; the contribution of age to post ischemic inflammation has been understudied. Aging is a non-modifiable risk factor for stroke and is a critical determinant to stroke outcome. Since 75-89% of strokes occur in the elderly, it is important to characterize the differential effects of aging on the inflammatory response to stroke before translation of immunomodulatory therapeutic strategies into the clinic. Therefore, the objective of this study was to study the impact of aging on post s troke inflammatory milieu of the brain . Methods- Young(6 months), aging(15 months) and aged(22 months) male and female mice were subjected to 60 minutes of MCAO (n=5-6/ group). The ischemic hemisphere was subjected to mechanical and enzymatic digestion and then brain mononuclear cells were harvested at the 30%-60% interphase of percoll gradient. Cells were stained with fluorophore conjugated antibodies for CD45,CD3,CD11b and Gr1 and counted on LSRII cytometer(BD Biosciences). Results- Blood derived leukocytes(CD45high) increased in the brain in stroke(7133+−4514) vs. sham(1081+−279.9). We found a significant main effect of age, F(2,38)=5,p<0.05 and stroke, F(2,38)=19.5,p<0.01 in the percentage of T cells(CD45highCD3+). There was also a significant age by stroke interaction in the percentage of T cells, F(2,38)=0.58,p<0.05. In the CD45intermediateCD11b+ microglia population, we saw a significant main effect of stroke, F(1,38)=18.6,p<0.01 (sham 19199.2+−3439 vs. stroke 38365.4+−1111 ). Similarly, there was a significant main effect of stroke on CD45intermediate/CD11b+/Gr1+ microglia numbers, F(1,38)=12.6,p<0.01 . Conclusions- T cells, microglia and Gr1+ microglia numbers increase in the brain after an ischemic stroke. However, only the CD45hiCD3+T cells significantly increased in the aging brain after an ischemic insult in the two sexes. Microglia and Gr1+microglia did increase after stroke in both sexes, but there was no significant effect of age. Our study suggests that aging creates a differential inflammatory milieu in the brain after an ischemic event and that elderly mount a profound T cell response to stroke. Since most of our stroke patients are old, bench to clinic translation of stroke therapies needs to account for this heterogeneity in inflammatory response across different ages.