Enhancement of Heme-Oxygenase 1 in the Injured Peripheral Nerve Following Sulforaphane Administration Fosters Regeneration via Proliferation and Maintenance of Repair Schwann Cells
Fabian Szepanowski,
Jaqueline Zipfel,
Rebecca D. Szepanowski,
Bianca Eggert,
Nail-Mert Güner,
Leon-Phillip Szepanowski,
Christoph Kleinschnitz,
Anne K. Mausberg,
Mark Stettner
Affiliations
Fabian Szepanowski
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Jaqueline Zipfel
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Rebecca D. Szepanowski
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Bianca Eggert
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Nail-Mert Güner
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Leon-Phillip Szepanowski
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Christoph Kleinschnitz
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Anne K. Mausberg
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Mark Stettner
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
Nuclear erythroid 2-related factor 2 (Nrf2) and its downstream effector heme oxygenase 1 (HO-1) are commonly activated in response to cellular stresses. The elevated expression of HO-1 has been associated with markedly accelerated peripheral nerve regeneration. This study aimed to evaluate the impact of a naturally occurring dietary Nrf2/HO-1 activator—sulforaphane (SFN)—on regeneration in a murine sciatic nerve crush model. The beneficial safety profile of SFN has been thoroughly investigated and confirmed several times. Here, SFN was administered daily, starting immediately after C57BL/6 mice were subjected to sciatic nerve crush injury. Injured sciatic nerves were excised at various time points post injury for molecular, immunohistochemical and morphometric analyses. Moreover, functional assessment was performed by grip strength analysis and electrophysiology. Following SFN treatment, the early response to injury includes a modulation of autophagic pathways and marked upregulation of Nrf2/HO-1 expression. This enhancement of HO-1 expression was maintained throughout the regeneration phase and accompanied by a significant increase in repair Schwann cells. In these cells, elevated proliferation rates were observed. Significant improvements in grip strength test performance, nerve conduction velocity and remyelination were also noted following SFN treatment. Collectively, SFN modulates cytoprotective and autophagic pathways in the injured nerve, increasing the number of repair Schwann cells and contributing to effective nerve regeneration. Given the availability of SFN as a nutritional supplement, this compound might constitute a novel regenerative approach with broad patient accessibility and further studies on this topic are warranted.
