NF155-overexpression promotes remyelination and functional restoration in a hypoxic-ischemic mixed neonatal rat forebrain cell culture system.

White matter injury caused by perinatal hypoxia-ischemia is characterized by myelination disorders; however, its pathophysiological mechanisms are not fully elucidated. The neurofascin 155 (NF155) protein, expressed in oligodendrocytes, is critical for myelination. Previous findings suggest that NF155 participates in the pathological mechanisms of developmental myelination disorders in hypoxic-ischemic cerebral white matter lesions, and it might regulate cytoskeletal changes. Therefore, we hypothesized that increased NF155 expression during the early stages of hypoxic oligodendrocyte injury helps normalize myelin sheath development and consequently improves neural function by repairing paranodal structures of myelin sheaths and regulating cytoskeletal changes. To test this hypothesis, we established a hypoxic-ischemic, mixed neonatal rat forebrain cell culture model. When NF155 expression was upregulated, synergistic effects occurred between this protein and the paranodal proteins CASPR and contactin. In addition, the expression of Rho GTPase family proteins that regulate key cytoskeletal pathways, myelin sheath structures, and functions were restored, and axonal structures acquired a clear and transparent appearance. These results suggest that NF155 may enable myelin sheath repair by repairing paranodal region structures and regulating oligodendrocyte cytoskeletal mechanisms. Overall, the present study provides new insights into the pathogenesis of hypoxic-ischemic cerebral white matter lesions.