title: Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study.
abstract: The cytokine interleukin-1beta (IL-1beta) is implicated in a broad spectrum of CNS pathologies, in which it is thought to exacerbate neuronal loss. Here, the effects of injecting recombinant rat IL-1beta into the striatum of 3-week-old rats were followed noninvasively from 2 to 123 hr using magnetic resonance imaging and spectroscopy. Four hours after injection of IL-1beta (1 ng in 1 microliter), cerebral blood volume was significantly increased, the blood-brain barrier (BBB) became permeable to intravenously administered contrast agent between 4.5 and 5 hr, and the apparent diffusion coefficient (ADC) of brain water fell by 6 hr (5.42 +/- 0. 35 x 10(-4) mm(2)/sec treated, 7.35 +/- 0.77 x 10(-)(4) mm(2)/sec control; p < 0.001). At 24 hr the BBB was again intact, but the ADC, although partially recovered, remained depressed at both 24 and 123 hr (p < 0.03). Depleting the animals of neutrophils before IL-1beta injection prevented the BBB permeability at all time points, but the ADC was still depressed at 6 hr (6.64 +/- 0.34 x 10(-4) mm(2)/sec treated, 7.49 +/- 0.38 x 10(-4) mm(2)/sec control; p < 0.005). No changes were seen in brain metabolites using proton spectroscopy at 6 hr after IL-1beta. Intraparenchymal injection of IL-1beta caused a neutrophil-dependent transient increase in BBB permeability. The presence of neutrophils within the brain parenchyma significantly contributed to the IL-1beta-induced changes in cerebral blood volume and the ADC of brain water. However, IL-1beta apparently had a direct effect on the resident cell populations, which persisted well after all recruited leukocytes had disappeared. Thus the action of IL-1beta alone can give rise to magnetic resonance imaging-visible changes that are normally attributed to alterations to cellular homeostasis.
authors.affiliation: Medical Research Council Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom. amb@bioch.ox.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Blamire
authors.forename: D C
authors.initials: DC
authors.lastname: Anthony
authors.forename: B
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: N R
authors.initials: NR
authors.lastname: Sibson
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
authors.forename: P
authors.initials: P
authors.lastname: Styles
mesh_terms: D000208:Acute Disease; D000818:Animals; D001810:Blood Volume / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D002452:Cell Count; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002908:Chronic Disease; D003287:Contrast Media; D003342:Corpus Striatum / Q000187:drug effects; D004058:Diffusion / Q000187:drug effects; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008845:Microinjections; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D003287:Contrast Media; D007106:Immune Sera; D007375:Interleukin-1; D011994:Recombinant Proteins