Interleukin-1β-induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study
Blamire, A.M., Anthony, D.C., Rajagopalan, B., Sibson, N.R., Perry, V.H. and Styles, P. (2000) Interleukin-1β-induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. Journal of Neuroscience, 20, (21), 8153-8159.
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The cytokine interleukin-1beta (IL-1β ) 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-1β (1 ng in 1 µl), 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 × 10-4 mm2/sec treated, 7.35 ± 0.77 × 10-4 mm2/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-1β injection prevented the BBB permeability at all time points, but the ADC was still depressed at 6 hr (6.64 ± 0.34 × 10-4 mm2/sec treated, 7.49 ± 0.38 × 10-4 mm2/sec control; p < 0.005). No changes were seen in brain metabolites using proton spectroscopy at 6 hr after IL-1β.
Intraparenchymal injection of IL-1β caused a neutrophil-dependent transient increase in BBB permeability. The presence of neutrophils within the brain parenchyma significantly contributed to the IL-1β -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-1β alone can give rise to magnetic resonance imaging-visible changes that are normally attributed to alterations to cellular homeostasis.
|Keywords:||interleukin-1β, magnetic resonance, diffusion, cerebral blood volume, neutrophil, depletion|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
|Date Deposited:||08 Aug 2008|
|Last Modified:||02 Mar 2012 13:10|
|Contributors:||Blamire, A.M. (Author)
Anthony, D.C. (Author)
Rajagopalan, B. (Author)
Sibson, N.R. (Author)
Perry, V.H. (Author)
Styles, P. (Author)
|Date:||1 November 2000|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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