title: ICAM-1 induction in the mouse CNS following irradiation.
abstract: Injury to the central nervous system (CNS) results in inflammation, increased trafficking of leukocytes into the CNS, induction of cytokines, and exacerbation of the primary injury. The increased trafficking of neutrophils into the CNS has been described following a number of injury models including stab, stroke, and excitotoxin-induced injury. This enhanced trafficking has largely been ascribed to the adhesion molecule intercellular adhesion molecule-1 (ICAM-1, CD54). In the current study, we wished to determine if the inflammation caused by irradiation of the CNS resulted in a similar induction of ICAM-1. C3H/HeJ mice were irradiated using gamma irradiation aimed over the right cerebral hemisphere. The relative induction of ICAM-1 mRNA levels was determined using quantitative RT-PCR 6 hours following irradiation with either 0, 5, 15, 25 or 35 Gy. ICAM-1 message was seen to exhibit a normal dose response curve with increasing mRNA levels seen at 15 Gy and higher. To determine the cellular distribution of the ICAM-1 protein following irradiation, mice were sacrificed at 4 hrs, 24 hrs, 48 hrs and 7 days following 25 Gy irradiation and the tissue was processed for ICAM-1 immunocytochemistry. ICAM-1 staining was seen to increase in both endothelial cells and astrocytes beginning as early as 4 hrs. The staining intensity continued to increase throughout the 7 day period observed. Together, these results suggest that irradiation of the CNS causes a rapid induction of both ICAM-1 mRNA and protein. This suggests that increased leukocyte trafficking into the CNS may exacerbate the inflammation induced by radiation injury.
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: S
authors.initials: S
authors.lastname: Kyrkanides
authors.forename: B K
authors.initials: BK
authors.lastname: Harvey
authors.forename: M K
authors.initials: MK
authors.lastname: O'Banion
authors.forename: J P
authors.initials: JP
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Rubin
authors.forename: J T
authors.initials: JT
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005720:Gamma Rays; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1