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MRI characterisation of a novel rat model of focal astrocyte loss

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Abstract

Blood-brain barrier (BBB) integrity is lost in several neurological conditions in which astrocytes are damaged. We studied 3-chloropropanediol-induced focal lesions, a toxicant that induces early astrocytic (but not neuronal) death followed by BBB leakage. T2-weighted images illustrate regional selectivity of the lesions, affected areas including the inferior colliculi and red nuclei. Gd-DTPA intensity quantified the degree of vascular leakage in the lesioned areas. MRI intensity in lesioned areas peaked at 2 days, correlating with BBB breakdown, and diminished thereafter, returning to pre-injection levels by 30 days in parallel with the return of astrocytes. T2 measurements were unchanged at 6 h, a time when astrocyte swelling is marked but the vasculature is intact, but increased at 2 days, consistent with cellular damage and BBB leakage. Gd-DTPA enhancement was also greatest at 2 days then decreased over the next 28 days, indicating a tracer-size-dependent rate of BBB repair. A simple model based on experimentally acquired data indicated that the vascular breakdown was the result of leakage of only a small percentage of blood vessels in the affected areas. Loss of astrocytes contributes to barrier loss, and restoration of astrocytes is needed for full barrier recovery.

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Author notes

  1. G. Mavroudis

    Present address: School of Biological and Biomedical Sciences, University of Durham, Science Laboratories, South Road, Durham, DH1 3LE, UK

Authors and Affiliations

  1. MRC Applied Neuroscience Group, School of Biomedical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK

    A. M. Brown, T. Lister & D. E. Ray

  2. Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK

    M. J. W. Prior

  3. MRC Toxicology Unit, University of Leicester, Leicester, UK

    G. Mavroudis

Authors
  1. M. J. W. Prior
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  2. A. M. Brown
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  3. G. Mavroudis
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  4. T. Lister
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  5. D. E. Ray
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Corresponding author

Correspondence to A. M. Brown.

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Prior, M., Brown, A., Mavroudis, G. et al. MRI characterisation of a novel rat model of focal astrocyte loss. MAGMA 17, 125–132 (2004). https://doi.org/10.1007/s10334-004-0065-5

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  • DOI: https://doi.org/10.1007/s10334-004-0065-5

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