Bringing CLARITY to gray matter atrophy

Area of Science:

• Neuroscience
• Immunology
• Biomedical Imaging

Background:

• Gray matter atrophy correlates with disability in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).
• The link between gray matter atrophy and spinal cord pathology in EAE remains unclear.

Purpose of the Study:

• To investigate the relationship between cortical volume changes and spinal cord axonal pathology in EAE.
• To establish correlations between in vivo MRI findings and ex vivo tissue analysis using CLARITY.

Main Methods:

• Experimental autoimmune encephalomyelitis (EAE) induced in Thy1.1-YFP mice.
• In vivo magnetic resonance imaging (MRI) of brains.
• Optical clearing of brains and spinal cords using Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY).
• 3D axonal tracing in spinal cords and analysis of cortical neuron morphology.

Main Results:

• EAE mice showed decreased cortical volumes and reduced layer V pyramidal neuron apical dendrite length.
• Significant axonal damage observed in spinal cords, including axonal ovoids and end bulbs.
• Direct correlation found between decreased cortical volume and the number of axonal end bulbs in the spinal cord.

Conclusions:

• This study establishes a direct relationship between cortical volume loss and spinal cord axonal pathology in EAE.
• The findings highlight the utility of combining MRI and CLARITY for studying neurodegenerative processes in animal models.
• This research provides novel insights into the neuropathological mechanisms underlying EAE and potentially MS.