Abstract WP242: Stabilizing Mast Cell Signaling From The Gut Mitigates Neuroinflammation In The Brain Post Stroke

Abstract

Background: Clinically, ~65% of stroke patients are left with functional impairments after stroke and 15% die shortly after their stroke. Increasing evidence suggests that peripheral inflammatory responses after stroke play an important role in determining neurological outcome. Mast cells (MCs) are one of the most rapid responders to injury. MCs release histamine (HA), a pro-inflammatory transmitter that enhances inflammation. Gut MCs are a major source of HA. Hypothesis: We hypothesize that aged animals stroke will lead to robust gut mucosal MC-activation and HA release, with subsequent gut disruption and inflammation. Stabilizing peripheral MCs will decrease peripheral/central inflammation, MC trafficking, and improve stroke outcomes. Methods: We used a reversible middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18mo) wild-type male mice to investigate the MC role in neuroinflammation post-stroke (PS). We stroke the aged animals and treated the animals with 25 mg/kg BW of cromolyn (MC stabilizer), oral gavage. Cromolyn was administered at 3-h, 10-h, 24-h and every other day PS. Positive control group that were stroked but treated only with saline. In total, four groups stroke and sham (surgery control), out of these animals one set received cromolyn and one set received saline. We sacrificed animals at 3-h, 24 –h and 3-days after cromolyn treatment post-stroke. Results: We found that cromolyn administration significantly reduced MC numbers in the brain at 24-hours (P<0.0051) and 3 days (P<0.0005) PS. In association with that we found behavioral changes with improved motor activity at 3-days post-stroke animals after cromolyn treatment. We also found that gut mast cells are significantly reduced after cromolyn treatment in the 24 hours and 3-days PS groups (P<0.01). Additionally, we found significant decrease in NDS at the 3-days PS animals which was not very prominent at 24-hours (P<0.0125). Conclusion: Our results show that preventing MC-HA release post-stroke possess clinical value in preventing neuroinflammation PS. Future studies will focus on IgE and FcεR1 due to its cross-linking role in activating MC-HA release.