title: Microglial-macrophage synthesis of tumor necrosis factor after focal cerebral ischemia in mice is strain dependent.
abstract: Commonly used inbred mouse strains display substantial differences in sensitivity to focal cerebral ischemia. Such differences can often be ascribed to differences in vascular anatomy. The authors investigated whether a contributing factor could be strain-related differences in cellular synthesis of the pleiotropic and potential neurotoxic cytokine tumor necrosis factor (TNF) in the border zone of and within the focal cerebral infarct. In all mouse strains investigated they found that TNF was synthesized by infarct and periinfarct infiltrating Mac-1 immunopositive microglia-macrophages. BALB/c mice, which developed the largest infarcts, contained significantly fewer TNF-producing microglia-macrophages compared with SJL and C57BL/6 mice at both 12 and 24 hours after permanent occlusion of the distal part of the middle cerebral artery. SJL mice developed larger infarcts than C57BL/6 mice, whereas the number of TNF-producing microglia-macrophages per infarct volume unit was comparable. Western blotting data confirmed the increased TNF levels in SJL mice compared with BALB/c and C57BL/6 mice. Furthermore, mice with 12-hour postischemic survival consistently contained two-to threefold more TNF-producing microglia-macrophages than mice with 24-hour survival. The data show that the magnitude of the cellular TNF response to cerebral ischemia is strain dependent, while the time-profile and the cellular sources of TNF are similar irrespective of genetic background. Furthermore, the lack of correlation between infarct size and cellular TNF response suggests that the functionally important TNF is produced in the very early phase (minutes to a few hours) after induction of ischemia, just as it raises the possibility that different mouse strains display different sensitivities to TNF.
authors.affiliation: Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Odense University, Denmark. kll@imbmed.sdu.dk
authors.forename: Kate Lykke
authors.initials: KL
authors.lastname: Lambertsen
authors.forename: Rikke
authors.initials: R
authors.lastname: Gregersen
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D020768:Middle Cerebral Artery; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha