Schwann Cell Remyelination in Neuromyelitis Optica: Implications for CNS Repair
Yong Guo1, Zi-Yu Chen2, Nicolas Madigan1, Anthony Windebank1, Robin Franklin2, Claudia Lucchinetti3
1Mayo Clinic, 2University of Cambridge, 3The University of Texas at Austin
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. 

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.

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.
10.1212/WNL.0000000000206321