Abstract Details

Title Schwann Cell Remyelination in Neuromyelitis Optica: Implications for CNS Repair

Topic Autoimmune Neurology

Presentation(s) S32 - Autoimmune Neurology: NMOSD/MOGAD (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background

In CNS remyelination, oligodendrocyte progenitor cells (OPCs) typically differentiate into oligodendrocytes to rebuild myelin sheaths around demyelinated axons. However, Schwann cells from the peripheral nervous system (PNS) can also contribute to this process, either migrating from the CNS or differentiating from OPCs. The extent of Schwann cell-driven CNS remyelination is influenced by reactive astrocytes, which can bias OPC differentiation towards oligodendrocytes and restrict PNS-derived Schwann cell involvement.

Objective

This study investigates Schwann cell-mediated remyelination in Neuromyelitis Optica (NMO), an autoimmune disorder compromising astrocyte function. We aim to assess the implications for central nervous system (CNS) repair.

Design/Methods

To comprehensively study Schwann cell-mediated remyelination in human CNS tissue, we conducted a detailed histopathological and immunohistochemical analysis. We analyzed 27 NMO CNS autopsy cases (358 blocks), 37 multiple sclerosis (MS) cases as disease controls (349 blocks), and 5 normal CNS autopsy cases (30 blocks).

Results

Our findings reveal significant Schwann cell-mediated remyelination in 19 out of 27 NMO cases, particularly in spinal cord and brain lesions. In contrast, Schwann cell remyelination was rare in MS patients, observed in only one spinal cord section. Schwann cell-mediated remyelination occurred across various CNS regions, including the spinal nerve root entry zone, subpial and subependymal areas, perivascular regions, and parenchyma. Importantly, some Schwann cell remyelination was found in astrocytic regions. Moreover, our study detected a significant loss of STAT3, critical for astrocytic activation in CNS injury response, in NMO lesions.

Conclusions This study reveals substantial Schwann cell-mediated remyelination in NMO patients, especially in regions without astrocytes. Suppressing astrocytic reactivity could offer a promising therapeutic avenue to harness Schwann cell-mediated CNS remyelination. These findings advance our understanding of CNS repair mechanisms and open doors for potential interventions in demyelinating CNS diseases.

Authors/Disclosures
Yong Guo PRESENTER	No disclosure on file
Zi-Yu Chen	No disclosure on file
Nicolas Madigan, MD	Dr. Madigan has nothing to disclose.
Anthony J. Windebank, MD, FAAN (Mayo Clinic)	Dr. Windebank has nothing to disclose.
Robin Franklin	No disclosure on file
Claudia F. Lucchinetti, MD, FAAN (University of De Medical School, Health Learning Blg)	The institution of Dr. Lucchinetti has received research support from Biogen Idec. The institution of Dr. Lucchinetti has received research support from NIH/NINDS. The institution of Dr. Lucchinetti has received research support from National Institute of Neurological Disorders and Stroke . The institution of Dr. Lucchinetti has received research support from National Multiple Sclerosis Society. The institution of Dr. Lucchinetti has received research support from National Center for Advancing Translational Sciences. Dr. Lucchinetti has received intellectual property interests from a discovery or technology relating to health care. Dr. Lucchinetti has a non-compensated relationship as a Member with National Institute of Neurological Disorders that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Board of Directors, Association of University Professors of Neurology that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Trustees that is relevant to AAN interests or activities. Dr. Lucchinetti has a non-compensated relationship as a Member with Mayo Clinic Board of Governors that is relevant to AAN interests or activities.