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Updated: Jun 26, 2025
Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice
Published on: March 1, 2017
Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed
Ege Anil Ucar1,2, Esra Ozkan1,3, Narges Shomalizadeh1
1Research Center for Translational Medicine (KUTTAM), Koҫ University, Istanbul, Türkiye.
Introduction:
Multiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX).
Methods:
PLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated.
Results:
In the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture.
Discussion:
The study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.
Insights
Carbenoxolone (CBX) reduces fibrosis and improves outcomes in multiple sclerosis (MS) models. This hemichannel blocker shows potential as a new therapy for MS, mitigating disease progression and demyelination.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a leading cause of disability in young adults, often presenting as relapsing-remitting MS (RRMS).
- Progressive MS leads to brain and spinal cord atrophy, increasing disability.
- Pericytes may play a role in fibrosis within the central nervous system in MS models.
Purpose of the Study:
- To investigate the role of pericytes in fibrosis formation in a multiple sclerosis model.
- To evaluate the therapeutic potential of Carbenoxolone (CBX), a hemichannel blocker, in mitigating fibrosis and disease progression.
Main Methods:
- Utilized the PLP-induced experimental autoimmune encephalitis (EAE) model for in-vivo studies.
- Assessed fibrosis by measuring Collagen 1 and 3 accumulation in the spinal cord.
- Developed an in-vitro model using human brain vascular pericytes (HBVP) incubated with MS patient sera.
Main Results:
- CBX treatment significantly reduced disease progression, demyelination, and fibrosis in the EAE model.
- Both intracerebroventricular and intraperitoneal administration of CBX were effective.
- CBX also mitigated MS-serum-induced fibrosis in the in-vitro HBVP model.
Conclusions:
- Carbenoxolone effectively decreases fibrosis formation in both in-vivo and in-vitro models of MS.
- CBX improves neurological scores and reduces demyelination in the EAE model.
- CBX represents a potential novel therapeutic strategy for treating Multiple Sclerosis.
