Interleukin-1β-Induced Changes in Blood–Brain Barrier Permeability, Apparent Diffusion Coefficient, and Cerebral Blood Volume in the Rat Brain: A Magnetic Resonance Study

• Published in: The Journal of neuroscience 2000-11, Vol.20 (21), p.8153-8159
• Main Authors: Blamire, A. M., Anthony, D. C., Rajagopalan, B., Sibson, N. R., Perry, V. H., Styles, P.
• Format: Article
• Language: English
• Subjects: interleukin 1^b
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.20-21-08153.2000

The cytokine interleukin-1β (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-1β 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 mm 2 /sec treated, 7.35 ± 0.77 × 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-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 mm 2 /sec treated, 7.49 ± 0.38 × 10 − 4 mm 2 /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-1β 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.