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The Journal of Neuroscience, November 1, 2000, 20(21):8153-8159
Interleukin-1 -Induced Changes in Blood-Brain Barrier
Permeability, Apparent Diffusion Coefficient, and Cerebral Blood Volume
in the Rat Brain: A Magnetic Resonance Study
A. M.
Blamire1,
D. C.
Anthony2,
B.
Rajagopalan1,
N. R.
Sibson1,
V. H.
Perry2, and
P.
Styles1
1 Medical Research Council Biochemical and Clinical
Magnetic Resonance Unit, Department of Biochemistry, University of
Oxford, Oxford OX1 3QU, United Kingdom, and 2 CNS
Inflammation Group, School of Biological Sciences, University of
Southampton, Southampton SO16 7PX, United Kingdom
The cytokine interleukin-1 (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-1
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-1 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.
Key words:
interleukin-1 ; magnetic resonance; diffusion; cerebral
blood volume; neutrophil; depletion
Copyright © 2000 Society for Neuroscience 0270-6474/00/20218153-07$05.00/0
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