title: No effect of ablation of surfactant protein-D on acute cerebral infarction in mice.
abstract: BACKGROUND
  Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice.
  
  
  METHODS
  The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively.
  
  
  RESULTS
  Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice.
  
  
  CONCLUSIONS
  SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had no effect on ischemic cerebral infarction.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lambertsen
authors.forename: Kamilla
authors.initials: K
authors.lastname: Østergaard
authors.forename: Bettina H
authors.initials: BH
authors.lastname: Clausen
authors.forename: Søren
authors.initials: S
authors.lastname: Hansen
authors.forename: Jan
authors.initials: J
authors.lastname: Stenvang
authors.forename: Stine B
authors.initials: SB
authors.lastname: Thorsen
authors.forename: Michael
authors.initials: M
authors.lastname: Meldgaard
authors.forename: Bjarne W
authors.initials: BW
authors.lastname: Kristensen
authors.forename: Pernille B
authors.initials: PB
authors.lastname: Hansen
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sorensen
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsloewsvej 25, 2, DK-5000 Odense C, Denmark. bfinsen@health.sdu.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens