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.