Interleukin-1?-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-1?-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.

Abstract

The cytokine interleukin-1beta (IL-1? ) 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-1? (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-1? 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-1?.
Intraparenchymal injection of IL-1? caused a neutrophil-dependent transient increase in BBB permeability. The presence of neutrophils within the brain parenchyma significantly contributed to the IL-1? -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-1? alone can give rise to magnetic resonance imaging-visible changes that are normally attributed to alterations to cellular homeostasis.

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