title: Cerebral mast cells regulate early ischemic brain swelling and neutrophil accumulation.
abstract: We previously observed degranulated mast cells (MC) in association with perivascular brain edema formation during focal cerebral ischemia. Brain MC are typically located perivascularly and contain potent fast-acting vasoactive and proteolytic substances. We examined in a rat model of transient middle cerebral artery occlusion (MCAO) whether, in the early phase of ischemia, MC regulate microcirculation, the blood-brain barrier (BBB) permeability, and edema formation. First, animals received MC inhibitor (cromoglycate), MC-degranulating drug (compound 48/80), or saline. Thereafter, we performed transient MCAO in gene-manipulated MC-deficient rats and their wild-type (WT) littermates, calculating brain swelling, visualizing BBB leakage by intravenously administered Evans blue albumin, and determining neutrophil infiltration with light microscopy. Cerebral blood flow, monitored by laser-Doppler flowmetry in separate experiments, was similar among pharmacological treatments. Ischemic swelling resulted in increased hemispheric volume of 13.4%+/-1.0% in controls, 8.1%+/-0.4% (39% reduction) after cromoglycate, and 25.2%+/-2.0% (89% increase) after compound 48/80 (P<0.05). Early ischemic BBB leakage was reduced by 51% after cromoglycate, and 50% enhanced by compound 48/80 (P<0.05). The cromoglycate group showed 37% less postischemic neutrophil infiltration than did controls (P<0.05). Furthermore, MC-deficient rats responded to focal ischemia with 58% less brain swelling (6.7%+/-1.2%) than did their WT littermates (15.8%+/-1.4%, P<0.05). Blood-brain barrier damage was 47% lower in MC-deficient rats than in the WT (P<0.05). Neutrophil infiltration after MCAO was decreased 47% in MC-deficient rats in comparison to WT (P<0.05). Pharmacological MC inhibition thus appears to deserve further investigation regarding reduction of brain swelling and inflammation early after stroke.
authors.affiliation: Department of Neurology, Helsinki University Central Hospital and Neuroscience Program, University of Helsinki, Helsinki, Finland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Strbian
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Karjalainen-Lindsberg
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.forename: Perttu J
authors.initials: PJ
authors.lastname: Lindsberg
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000473:pathology / Q000502:physiology; D001929:Brain Edema; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D004205:Cromolyn Sodium / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D017078:Laser-Doppler Flowmetry; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008833:Microcirculation; D009504:Neutrophils / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D018927:Anti-Asthmatic Agents; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium