ORC ID , Monika von Düring2, David Lutz2, Maja Vulović3, Mohammad Hamad1, Gebhard Reiss1, Eckart Förster2, Melitta Schachner PhD 4 ORC ID ">
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RESEARCH ARTICLE
Year : 2022  |  Volume : 17  |  Issue : 8  |  Page : 1802-1808

Mice lacking perforin have improved regeneration of the injured femoral nerve


1 Institut für Anatomie und Klinische Morphologie, Universität Witten/Herdecke, Witten, Germany
2 Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany
3 Department of Anatomy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4 Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA

Correspondence Address:
Igor Jakovcevski
Institut für Anatomie und Klinische Morphologie, Universität Witten/Herdecke, Witten
Germany
Melitta Schachner
Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ
USA
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Source of Support: This study was supported by the Li Kashing Foundation (to MS), the FoRUM grant F957N-2019 of the Ruhr-University Bochum (to DL), and the Heinrich und Alma Vogelsang Stiftung (to IJ), Conflict of Interest: None


DOI: 10.4103/1673-5374.332152

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The role that the immune system plays after injury of the peripheral nervous system is still not completely understood. Perforin, a natural killer cell- and T-lymphocyte-derived enzyme that mediates cytotoxicity, plays important roles in autoimmune diseases, infections and central nervous system trauma, such as spinal cord injury. To dissect the roles of this single component of the immune response to injury, we tested regeneration after femoral nerve injury in perforin-deficient (Pfp–/–) and wild-type control mice. Single frame motion analysis showed better motor recovery in Pfp–/– mice compared with control mice at 4 and 8 weeks after injury. Retrograde tracing of the motoneuron axons regrown into the motor nerve branch demonstrated more correctly projecting motoneurons in the spinal cord of Pfp–/– mice compared with wild-types. Myelination of regrown axons measured by g-ratio was more extensive in Pfp–/– than in wild-type mice in the motor branch of the femoral nerve. Pfp–/– mice displayed more cholinergic synaptic terminals around cell bodies of spinal motoneurons after injury than the injured wild-types. We histologically analyzed lymphocyte infiltration 10 days after surgery and found that in Pfp–/– mice the number of lymphocytes in the regenerating nerves was lower than in wild-types, suggesting a closed blood-nerve barrier in Pfp–/– mice. We conclude that perforin restricts motor recovery after femoral nerve injury owing to decreased survival of motoneurons and reduced myelination.


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