Visualization of inflammation and demyelination in 2D2 transgenic mice with rodent MRI

Jordan C Bell1, Qingwei Liu, Yan Gan

  • 1Department of Neurology and BNI-ASU Center for Preclinical Imaging, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States.

Insights

New research tools are vital for differentiating neuromyelitis optica (NMO) and multiple sclerosis (MS). This study introduces a 2D2(tg) mouse model that develops optic and spinal cord lesions, aiding NMO research.

Area of Science:

  • Neuroimmunology
  • Neuroscience
  • Medical Imaging

Background:

  • Neuromyelitis optica (NMO) and multiple sclerosis (MS) present similar early symptoms, necessitating better research models.
  • Current research tools lack specificity for differentiating NMO and MS in early disease stages.

Purpose of the Study:

  • To characterize optic nerve and spinal cord lesions in 2D2(tg) mice using high-field-strength MRI.
  • To evaluate the potential of the 2D2(tg) mouse as a model for NMO research.

Main Methods:

  • High-field-strength magnetic resonance imaging (MRI) was used to analyze lesions in 2D2(tg) mice.
  • Immunohistology was performed to assess inflammatory infiltrates, demyelination, and aquaporin-4 (AQP4) protein levels at lesion sites.

Main Results:

  • Early Blood-brain Barrier (BBB) breakdown was detected in 86% of 2D2(tg) mice.
  • MRI-identified lesions correlated with inflammatory infiltrates and demyelination in the brain and spinal cord.
  • A decrease in AQP4 protein was observed at lesion sites, mirroring findings in NMO patients.

Conclusions:

  • 2D2(tg) mice develop optic and spinal cord lesions detectable by high-field rodent MRI and pathological assessment.
  • The characterized lesions in 2D2(tg) mice resemble those in human NMO patients.
  • The 2D2(tg) mouse model shows promise for advancing NMO research.

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