title: Cranial irradiation leads to acute and persistent neuroinflammation with delayed increases in T-cell infiltration and CD11c expression in C57BL/6 mouse brain.
abstract: Radiotherapy is commonly employed to treat cancers of the head and neck and is increasingly used to treat other central nervous system (CNS) disorders. Exceeding the radiation tolerance of normal CNS tissues can result in sequelae contributing to patient morbidity and mortality. Animal studies and clinical experience suggest that neuroinflammation plays a role in the etiology of these effects; however, detailed characterization of this response has been lacking. Therefore, a dose-time investigation of the neuroinflammatory response after single-dose cranial irradiation was performed using C57BL/6 mice. Consistent with previous reports, cranial irradiation resulted in multiphasic inflammatory changes exemplified by increased transcript levels of inflammatory cytokines, along with glial and endothelial cell activation. Cranial irradiation also resulted in acute infiltration of neutrophils and a delayed increase in T cells, MHC II-positive cells, and CD11c-positive cells seen first at 1 month with doses ≥ 15 Gy. CD11c-positive cells were found almost exclusively in white matter and expressed MHC II, suggesting a "mature" dendritic cell phenotype that remained elevated out to 1 year postirradiation. Our results indicate that cranial irradiation leads to persistent neuroinflammatory changes in the C57BL/6 mouse brain that includes unique immunomodulatory cell populations.
authors.affiliation: Department of Neurobiology and Anatomy and, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moravan
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000528:radiation effects; D001835:Body Weight / Q000528:radiation effects; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D039521:CD11c Antigen / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects; D042783:Endothelial Cells / Q000473:pathology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology / Q000528:radiation effects; D009336:Necrosis / Q000209:etiology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000528:radiation effects; D009504:Neutrophils / Q000276:immunology / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012886:Skull / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D013997:Time Factors
chemical_list: D039521:CD11c Antigen; D018836:Inflammation Mediators; D012333:RNA, Messenger