Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation

Abstract

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 the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1 GFP 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 where they are closely associated with areas of demyelination, myeloid cell 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.

Progressive Multifocal Leukoencephalopathy Mimicking Malignancy on 68Ga-FAPI PET/CT

“…The increase FAPI activity in PML may be related to the repair response after JCV infects oligodendrocytes. [11][12][13][14] Progressive multifocal leukoencephalopathy should be differentiated from multiple brain metastases and high-grade glioma on 68 Ga-FAPI PET/CT. 10,15 Our case also suggests the potential usefulness of 68 Ga-FAPI PET/CT for the early diagnosis, early treatment, and prognostication of PML.…”

“…In this case, all involved cerebral white matter showed increased FAPI activity. The increase FAPI activity in PML may be related to the repair response after JCV infects oligodendrocytes [11][12][13][14]. Progressive multifocal leukoencephalopathy should be differentiated from multiple brain metastases and high-grade glioma on 68 Ga-FAPI PET/CT 10,15.…”