Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord Chato Astrain, Jesús Roda Murillo, Olga Sánchez Porras, David Alaminos Mingorance, Miguel Campos Sánchez, Fernando García García, Óscar Darío Carriel Araya, Víctor Growth-associated protein 43 (GAP-43) Immunohistochemistry Nerve guide Nerve tissue regeneration Peripheral nerve repair Spinal cord Tissue engineering The study was financed by the Spanish "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Economia y Competitividad (Instituto de Salud Carlos III)", grant Nos: FIS PI17-0393, FIS PI20-0318, co-financed by the "Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union"; grant No. P18-RT-5059 by "Plan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI 2020), Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia, Espana"; and grant No. A-CTS-498-UGR18 by "Programa Operativo FEDER Andalucia 2014-2020, Universidad de Granada, Junta de Andalucia, Espana", co-funded by ERDF-FEDER, the European Union (all to VC). Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling. We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation. Conversely, the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression. However, central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker. In this study, we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems. First, histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards. The growth-associated protein 43 expression profile varied across regions and follow-up times, from a localized expression to an abundant and consistent expression throughout the regeneration tissue, confirming the presence of an active nerve regeneration process. Second, spinal cord changes were also histologically assessed, and no apparent changes in the structural and cellular organization were observed using routine staining methods. Surprisingly, remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level, in particular at 20 days post-repair and beyond. Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord. These findings differed from the growth-associated protein 43 pattern observed in the healthy control, which did not express growth-associated protein 43 at these levels. Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection. These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury. 2023-09-25T09:41:00Z 2023-09-25T09:41:00Z 2023-08 journal article Chato-Astrain J, Roda O, Sánchez-Porras D, Miralles E, Alaminos M, Campos F, García-García ÓD, Carriel V (2023). Peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord. Neural Regen Res 18(8):1852-1856. [https://doi.org/10.4103/1673-5374.363180] https://hdl.handle.net/10481/84627 10.4103/1673-5374.363180 eng http://creativecommons.org/licenses/by-nc-sa/4.0/ open access Atribución-NoComercial-CompartirIgual 4.0 Internacional Wolters Kluwer Medknow Publications