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Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis

Susanna Ricci, Denis Grandgirard, Michael Wenzel

    BMC Infectious Diseases
    |January 1, 2015
    PubMed
    Abstract

    Insights

    Matrix metalloproteinases (MMPs) contribute to brain damage from meningococcal meningitis (MM). Inhibiting MMPs with batimastat (BB-94) reduced brain injury and blood-brain barrier breakdown in a mouse model of MM.

    Area of Science:

    • Neuroscience
    • Infectious Diseases
    • Pharmacology

    Background:

    • Meningococcal meningitis (MM) survivors face neurological deficits due to brain damage.
    • Matrix metalloproteinases (MMPs) are implicated in MM-induced brain injury.

    Purpose of the Study:

    • Investigate the role of MMPs in a novel mouse model of MM-induced brain damage.
    • Evaluate the therapeutic potential of MMP inhibition.

    Main Methods:

    • Developed a mouse model of MM using intracisternal infection with Neisseria meningitidis.
    • Administered the MMP inhibitor batimastat (BB-94) or vehicle to infected mice.
    • Assessed survival, brain injury, and biomarkers 48 hours post-infection.

    Main Results:

    • Batimastat treatment significantly reduced MMP-9 levels, intracerebral bleeding, and blood-brain barrier (BBB) breakdown.
    • MMP-9 levels strongly correlated with intracerebral hemorrhage and BBB disruption in MM mice.

    Conclusions:

    • MMPs play a significant role in brain damage during experimental MM.
    • MMP inhibition offers a potential strategy to mitigate intracranial complications and sequelae of MM.

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