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Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
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MMP9 deficiency does not decrease blood-brain barrier disruption, but increases astrocyte MMP3 expression during

Carine Savarin1, Stephen A Stohlman, Anna M Rietsch

  • 1Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Glia
|July 30, 2011
PubMed

Insights

Neutrophil matrix metalloproteinase-9 (MMP9) is not essential for blood-brain barrier disruption in viral encephalomyelitis. Astrocytes upregulate MMP3 in MMP9-deficient mice, suggesting collaborative roles in regulating brain inflammation.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Virology

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP9, are linked to blood-brain barrier (BBB) disruption in neuroinflammatory conditions.
  • During JHMV infection, MMP9 activity is primarily observed in neutrophils, suggesting a role in leukocyte infiltration.

Purpose of the Study:

  • To investigate the necessity of MMP9 in BBB disruption and leukocyte infiltration during JHMV-induced encephalomyelitis.
  • To explore the compensatory roles of other MMPs, like MMP3, in the absence of MMP9.

Main Methods:

  • Utilized JHMV-infected MMP9-deficient (MMP9(-/-)) and wild-type (WT) mice.
  • Assessed leukocyte infiltration, BBB integrity, and MMP expression patterns (MMP3, MMP9) in the central nervous system (CNS).
  • Investigated the impact of neutrophil depletion on CNS leukocyte accumulation.

Main Results:

  • MMP9 deficiency did not alter BBB disruption or CNS leukocyte infiltration in JHMV-infected mice compared to WT.
  • Neutrophil depletion reduced monocyte and T cell accumulation but did not affect overall pathogenesis.
  • MMP9 deficiency led to increased MMP3 expression in astrocytes, suggesting a compensatory mechanism.

Conclusions:

  • Neutrophil-derived MMP9 is not the sole mediator of BBB disruption and leukocyte entry into the CNS during viral encephalomyelitis.
  • Astrocytes play a significant role in regulating BBB permeability, potentially collaborating with infiltrating immune cells.
  • Targeting individual MMPs for therapeutic intervention in neuroinflammation may be complex due to compensatory mechanisms.

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