Mice lacking perforin have improved regeneration of the injured femoral nerve

查看全文 作　　者：Igor [1]Jakovčevski;Monika von [2]Düring;David [2]Lutz;Maja [3]Vulović;Mohammad [1]Hamad;Gebhard [1]Reiss;Eckart [2]Förster;Melitta [4]Schachner 机构地区：[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 出　　处：《Neural Regeneration Research》索引2022年第17卷第8期,共7页 基　　金：supported by the Li Kashing Foundation(to MS);the FoRUM grant F957N-2019 of the Ruhr-University Bochum(to DL);the Heinrich und Alma Vogelsang Stiftung(to IJ). 摘　　要：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. 关 键 词：blood-nerve barrier femoral nerve injury locomotor recovery LYMPHOCYTES MYELINATION NK-cells PERFORIN REINNERVATION