En J. Galli,zyyzz Tonya M. Bliss,*yz and Gary K. Steinberg*yzFrom the Departments of Neurosurgery,* Pathology,yy Microbiology and Immunology,zz and Biochemistry,** the Stanford Stroke Center,y along with the Stanford Institute for Neuro-Innovation and Translational Neurosciences,z School of Medicine, Stanford University, Stanford, California; the Division of Human Immunology,x Center for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia; the College of Molecular Biomedical Science,{ University of Adelaide, Adelaide, South Australia, Australia; and the Department of Molecular Biology and Center of Molecular Biology “Severo Ochoa”,k Universidad Autonoma de Madrid, Madrid, Spain Accepted for publication June 4, 2014. Address correspondence to Tonya M. Bliss, Ph.D., Department of Neurosurgery, 1201 Welch Rd., Stanford, CA 94035-5487; or Gary K. Steinberg, M.D., Ph.D., Department of Neurosurgery, 300 Pasteur Dr., R301A, Stanford, CA 94305-5325; or Stephen J. Galli, M.D., Department of Pathology, L-235, 300 Pasteur Dr., Stanford, CA 94305-5324; or Michele A. Grimbaldeston, Ph.D., Centre for Cancer Biology, IMVS Bldg., University of South Australia, Frome Rd., Adelaide, S. Australia 5000. E-mail: tbliss1@stanford. edu or [email protected] or sgalli@ stanford.edu or michele.grimbaldeston@unisa. edu.au.Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology.Omadacycline Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges.Octreotide With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology.PMID:24065671 These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. (Am J Pathol 2014, 184: 2493e2504; http://dx.doi.org/10.1016/j.ajpath.2014.06.003)Stroke, the leading cause of adult disability and the fourth most common cause of death in the Unites States,1,2 occurs when there is insufficient blood flow to the brain, and the resultant injury initiates a cascade of inflammatory events, including immune cell infiltration into the brain.3e5 This post-stroke inflammation is a critical determinant of damage and recovery after stroke; understanding the interplay between the immune system and the brain after stroke holds much promise for therapeutic intervention.4e7 However, successfully exploiting this therapeutic potential requires a detailed understanding of the interplay between the immune system and the brain after stroke.4 An understudied but important aspect of this interplay is the role of meningeal-located immune cells in modulating brain pathology. The meninges have long been recognizedCopyright 2.