Mast cell stabilization limits hypoxic-ischemic brain damage in the immature rat.
Perinatal hypoxic-ischemic (HI) brain damage is a major cause of mortality and neurological morbidity in infants and children. Using an established model of unilateral hypoxia-ischemia in neonatal rats, the present study focused on mast cells (MCs), important regulators of inflammatory processes, as potential contributors to HI damage. MCs are present in the pia of the neonatal rat, entering the central nervous system (CNS) during cerebral development along penetrating blood vessels. Following hypoxia-ischemia, MC numbers increased dramatically in the ipsilateral (ischemic) hemisphere (p < 0.01). In animals exposed to hypoxia only, the numbers of MCs were elevated in both hemispheres to an extent equal to that observed in the contralateral hemisphere of HI animals (p < 0.05 vs. control). Within damaged areas (ipsilateral only), MCs were observed in regions of activated microglia and astroglia that characterize the ischemic hemisphere. Using a triple-label paradigm, MCs were observed along elongating blood vessels, some of which express the GLUT1 isoform of the glucose transporter protein, indicative of blood-brain barrier vessels. To determine whether MC activation has a role in HI brain damage, rat pups were treated with the MCs stabilizer, disodium cromoglycate (cromolyn), prior to and/or following hypoxia-ischemia. The cromolyn treatment inhibited MC migration into the CNS (p < 0.05) and limited brain damage more than 50% (p < 0.01) vs. saline controls. These data support the hypothesis that MCs are key contributors to the extent of brain damage due to hypoxia-ischemia in the immature animal.
Jin
Yuxuan
Y
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA. yj2116@columbia.edu
Silverman
Ann-Judith
AJ
Vannucci
Susan J
SJ
D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001720:Birth Injuries / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004205:Cromolyn Sodium / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism; D005911:Gliosis / Q000276:immunology / Q000503:physiopathology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D051272:Glucose Transporter Type 1; C495679:Slc2a1 protein, rat; D004205:Cromolyn Sodium