Nimodipine Reduces Dysfunction and Demyelination in Models of Multiple Sclerosis

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Multiple sclerosis (MS) relapse treatment remains limited, with steroids offering little benefit for residual disability.
• Acute functional loss in MS models is linked to central nervous system (CNS) hypoxia.
• The precise cause of CNS hypoxia and its relation to vascular perfusion deficits require further investigation.

Purpose of the Study:

• Investigate the cause of hypoxia in experimental autoimmune encephalomyelitis (EAE), a model for MS.
• Determine if impaired vascular perfusion contributes to CNS hypoxia.
• Explore nimodipine, a CNS-selective vasodilator, as a potential therapy to restore function and prevent demyelination in MS models.

Main Methods:

• Assessed cardiovascular physiology, spinal oxygenation, mitochondrial function, and tissue perfusion in EAE models.
• Utilized a variety of established measurement techniques.

Main Results:

• Tissue hypoxia in EAE models was strongly associated with hypoperfusion of the inflamed spinal cord.
• Nimodipine treatment effectively restored spinal oxygenation and rapidly improved neurological function.
• Nimodipine therapy demonstrated a reduction in demyelination in both EAE and early MS lesion models.

Conclusions:

• Tissue hypoxia, stemming from spinal hypoperfusion, contributes to functional loss and demyelination in MS.
• Therapies enhancing blood flow, such as nimodipine, can protect neurological function and mitigate demyelination.
• Nimodipine presents a promising candidate for repurposing to provide significant clinical benefits in multiple sclerosis management.