Interleukin-1β-Induced Changes in Blood–Brain Barrier Permeability, Apparent Diffusion Coefficient, and Cerebral Blood Volume in the Rat Brain: A Magnetic Resonance Study
Open Access
- 1 November 2000
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 20 (21) , 8153-8159
- https://doi.org/10.1523/jneurosci.20-21-08153.2000
Abstract
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 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-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.Keywords
This publication has 56 references indexed in Scilit:
- Evaluation of extra‐ and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMRMagnetic Resonance in Medicine, 1998
- CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood–brain barrier breakdownCurrent Biology, 1998
- Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNSJournal of Neuroimmunology, 1998
- Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood–brain barrier breakdown in vivoNeuroscience, 1998
- Interleukin-1 Modulates Protein Tyrosine Phosphatase Activity and Permeability of Brain Endothelial CellsBiochemical and Biophysical Research Communications, 1997
- Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in ratsBrain, 1997
- EVIDENCE FOR AN EARLY INFLAMMATORY RESPONSE IN THE CENTRAL NERVOUS SYSTEM OF MICE WITH SCRAPIENeuroscience, 1996
- The influence of cytokines on the integrity of the blood-brain barrier in vitroJournal of Neuroimmunology, 1996
- An experimental model system for HIV-1-induced brain injuryAdvances in Neuroimmunology, 1994
- Rapid NMR imaging of dynamic processes using the FLASII techniqueMagnetic Resonance in Medicine, 1986