Abstract TP435: Junctional Adhesion Molecule-a Deficiency Attenuate Leukocytes Trafficking And Inflammation In Brain Ischemic /reperfusion Injury
Background: Brain ischemic reperfusion (I/R) injury elicits an intense inflammatory response that causes secondary brain damage. Proinflammatory mediators trigger intensive inflammatory remodeling of the blood-brain barrier (BBB) that includes extensive changes of the brain endothelial cell surface and alteration of junctional complex in order to “receive and support” leukocyte migration into the brain parenchyma. Junctional adhesion molecule-A (JAM-A) is component of the brain endothelial junctional complex with dual role: the occlusion of the paracellular route and regulation of leukocyte docking and migration. In this study we have examined contribution of JAM-A in developing the postischemic inflammatory response.
Method: Brain I/R injury was induced by transient occlusion of middle cerebral artery (tMCAO) for 30 min followed by reperfusion for 0-7 days. JAM-A role in brain I/R injury was investigated in condition of presence JAM-A on brain endothelial cells, JAM-A absence (JAM-A knockout -KO- mice) or in condition of inhibition via administration of JAM-A antagonist peptide (JAM-Ap, 1mg/ml), 6 hrs after tMCAO and for 6 consecutive days. Leukocytes infiltration was estimated by FACS analysis. The inflammatory mediators expression was evaluated by protein array, RT-PCR and ELISA.
Result: I/R-induced neutrophilstransmigration was attenuated in both JAM-A-KO mice as well as in mice treated with JAM-Ap whereas transmigration of monocytes and T cells was JAM-A independent. Consequently with that, expression of inflammatory mediators was reduced in area of penumbra. JAM-A-KO and mice treated with JAM-Ap showed the reduction of infarct size and significantly improved neurological score. BBB permeability was reduced by the treatment with JAM-Ap.
Conclusion: JAM-A has a prominent role in regulation of neutrophils infiltration after brain I/R injury and could be a new target in limiting thepostischemic inflammation.
- © 2012 by American Heart Association, Inc.