Neurorehabilitation and white matter repair in traumatic spinal cord injury: a dialog between clinical and preclinical studies

Vito Antonio Baldassarro¹Ilaria Baroncini²Laura Calza^3*Francesca Ciardulli²Luca Lorenzini¹Francesco Giuseppe Materazzi²Francesca Merighi⁴Corinne Quadalti³Lucia Ricci²Francesca Serafino²Laura Simoncini²

• ¹Department of Veterinary Medical Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy
• ²Montecatone Rehabilitation Institute, Imola, Italy
• ³Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Emilia-Romagna, Italy
• ⁴CIRI-SDV, Bologna, Emilia-Romagna, Italy

Central nervous system (CNS) has very limited repair capabilities, and the functional adaptation/compensation after acute injuries is attributed to the great plasticity of neural circuits, in particular at synaptic level. However, neurons are only one of the cellular components of the CNS, being the grey matter (GM) around 50%, compared to the white matter (WM), where oligodendrocytes (OLs), forming the myelin sheath, guarantee the isolation of axons for proper electrical conductivity elicited by action potential. WM is characterized by two remarkable properties: myelin plasticity, defined as experience-induced changes in myelination mediating long-lasting changes in neural circuit function, and myelin repair, that can be complete and functionally effective and represent the only true reparative capability of the CNS. Oligodendrocyte precursor cells (OPCs), accounting for 5-8% of the total CNS cells, are responsible for myelin plasticity and repair. OPCs are generated during development, widely distributed across the white and grey matter, and remain quiescent until appropriate stimuli, such as a functional request or an injury. In these conditions, endogenous OPCs, but also new OPCs derived from endogenous neural stem cells proliferation and differentiation, migrate towards axons, differentiate into mature OLs capable of wrapping axons and forming the myelin sheaths. In this review article, we discuss WM plasticity and myelin repair by OPC-dependent endogenous regeneration in the context of spinal cord injury (SCI) and related neurorehabilitation approaches. The clinical data, such as imaging data, concern the changes in the WM during the different phases of SCI and have been collected in different rehabilitation contexts. Preclinical data focus on physical stimuli able to improve the myelin repair capability of OPCs in the context of oligo-axon unit. The possible role of myelin regeneration by endogenous stem/precursor cells is finally discussed in the context of regenerative neurorehabilitation for SCI.