Abstract W P98: Monocyte Chemotactic Protein-3 Elevated in Stoke and Aging
Background: It is now recognized that stroke is a systemic stressor that triggers profound changes throughout the body, leading to alterations in the immune system and response. In the CNS, cell death from ischemic stroke activates glial cells, leading to trafficking of leukocytes into the brain and subsequent inflammation. Chemokines play an active role in modulating this recruitment process. Monocyte chemotactic protein-3 (MCP-3), also known as CCL7, is a chemokine that attracts a broad spectrum of immune cells. Although secreted at lower levels than the better-understood monocyte chemotactic protein-1, MCP-3 is released after injury and regulates migration of leukocytes, thus facilitating inflammation. As neuroinflammation is a well-documented complication after ischemic stroke, we hypothesized that MCP-3 levels would be elevated after stroke. In light of the fact that age is the principle risk factor for stroke, and that a chronic pro-inflammatory milieu is associated with aging, we also hypothesized that MCP-3 would increase with age.
Methods: Young (10 weeks) and aged (18 months) male C57B16 mice were subjected to transient (60 minute) middle cerebral artery occlusion (MCAO) or a sham surgery. MCP-3 protein levels in brain tissue and serum samples from these stroked mice, as well as from cohorts of young and aged naïve mice, were analyzed with an ELISA.
Results: The comparisons of naïve aged (n=4, mean=0.042±0.005 pg/μg) to naïve young (n=4, mean=0.017±0.009 pg/μg) mice showed a significant increase (p<.01) in MCP-3 in aged brain tissue. Additionally, when comparing aged MCAO to young MCAO (n=3, mean=0.01±0.007 pg/μg), MCP-3 was significantly elevated (p<.01) in the aged group. In comparing aged MCAO (n=6, mean=0.31±0.11 pg/ug ) to aged sham (n=6, mean=0.03±0.006 pg/μg), MCP-3 was significantly elevated (p<.05). No significant differences in MCP-3 levels in serum or between young stroke and young sham brain were seen.
Conclusions: We demonstrated that levels of MCP-3 are increased post-stroke in aged mice, but not in young mice. Given what is known about the role of MCP-3 in immune cell trafficking, our data imply that MCP-3 plays a role in inflammation post-stroke, and that it also primes the aged brain for a greater inflammatory response post-stroke.
Author Disclosures: C.A. Townshend: None. E.C. Koellhoffer: None. J. Grenier: None. A. Chauhan: None. S. DiMauro: None. V. Venna: None. L.D. McCullough: None.
- © 2015 by American Heart Association, Inc.