Publication Date




Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Neuroscience (Medicine)

Date of Defense


First Committee Member

Jae K. Lee

Second Committee Member

Roberta Brambilla

Third Committee Member

Vance Lemmon

Fourth Committee Member

Alejandro Caicedo


Remyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells (OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to an inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFP transgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset and infiltrate the parenchyma by the peak of behavioral deficits. Fibroblasts are closely associated with areas of demyelination, macrophage accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS.


Fibrosis; Fibroblasts; Oligodendrocytes; Regeneration; Experimental Autoimmune Encephalomyelitis; Multiple Sclerosis

Available for download on Thursday, July 29, 2021