{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:11:23Z","timestamp":1774613483712,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"crossref","award":["CF-214971"],"award-info":[{"award-number":["CF-214971"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["CBF-2025-G-1038"],"award-info":[{"award-number":["CBF-2025-G-1038"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PAPIIT-DGAPA-UNAM","award":["IN215522"],"award-info":[{"award-number":["IN215522"]}]},{"name":"PAPIIT-DGAPA-UNAM","award":["IN207524"],"award-info":[{"award-number":["IN207524"]}]},{"name":"PAPIIT-DGAPA-UNAM","award":["IN207624"],"award-info":[{"award-number":["IN207624"]}]},{"DOI":"10.13039\/501100003141","name":"CONAHCYT","doi-asserted-by":"crossref","award":["1083209"],"award-info":[{"award-number":["1083209"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003141","name":"CONAHCYT","doi-asserted-by":"crossref","award":["921788"],"award-info":[{"award-number":["921788"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondo Alejandro Bay\u00f3n"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Sciatic nerve injuries are among the most common classes of peripheral nerve harm and have a strong impact on quality of life, as well as a significant negative economic impact for patients, society, and governments, since they represent a frequent cause of work-related disabilities and sick leave applications. Following nerve injury, neurons, Schwann, and satellite cells undergo marked changes in phenotype, metabolic activity, neuronal survival, nervous transmission, and an exacerbated activation of the inflammatory response. Leuprolide acetate (LA), a clinically available agonist of gonadotropin-releasing hormone (GnRH), has shown clear neurotrophic properties and is considered a novel potential candidate for treating neural injuries, including sciatic nerve pathologies. This study aimed to analyze the effect of LA treatment on sensory function and dorsal root ganglia (DRG) changes in a rat sciatic nerve full-transection (SNT) model. Methods: Variations in cold and heat sensitivity were assessed using the thermal plate test, while DRG tissue sections were examined for modifications in reactive gliosis by immunofluorescence analysis, and axonal transport using a retrograde tracer. Also, changes in the expression of pro-regenerative genes Stat3, Socs3, Fos, Jun, Atf4, and Limk1 were quantified by qPCR. Results: Our results showed that LA treatment exerted a distinct neurotrophic effect, since it promoted the specific recovery of cold sensitivity, improved axonal transport, regulated the inflammatory response, and modulated the exacerbated expression of pro-regenerative genes in the SNT model. Conclusions: These findings indicate that LA therapy may have the potential to improve sensory recovery in patients with sciatic nerve injuries.<\/jats:p>","DOI":"10.3390\/brainsci16030332","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T09:44:41Z","timestamp":1773999881000},"page":"332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leuprolide Acetate Promotes Sensory Recovery and Modulates Dorsal Root Ganglion Responses After Sciatic Nerve Transection in Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-3684","authenticated-orcid":false,"given":"Irma","family":"Hern\u00e1ndez-Jasso","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Centro de Ciencias B\u00e1sicas, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4509-770X","authenticated-orcid":false,"given":"Denisse","family":"Calder\u00f3n-Vallejo","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Centro de Ciencias B\u00e1sicas, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"\u00c1vila-Mendoza","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Quer\u00e9taro 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8794","authenticated-orcid":false,"given":"David","family":"Epardo","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Quer\u00e9taro 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerusa","family":"Balderas-M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Quer\u00e9taro 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-8695","authenticated-orcid":false,"given":"Carlos","family":"Ar\u00e1mburo","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Quer\u00e9taro 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Quintanar","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Centro de Ciencias B\u00e1sicas, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-3413","authenticated-orcid":false,"given":"Carlos","family":"Mart\u00ednez-Moreno","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda Celular y Molecular, Instituto de Neurobiolog\u00eda, Campus Juriquilla, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Quer\u00e9taro 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.26502\/fjsrs0052","article-title":"Peripheral Nerve Regeneration: Opportunities and Challenges","volume":"5","author":"Supra","year":"2023","journal-title":"J. Spine Res. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11552-014-9692-0","article-title":"Social impact of peripheral nerve injuries","volume":"10","author":"Wojtkiewicz","year":"2015","journal-title":"Hand"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lopes, B., Sousa, P., Alvites, R., Branquinho, M., Sousa, A.C., Mendon\u00e7a, C., Atayde, L.M., Lu\u00eds, A.L., Varej\u00e3o, A.S., and Maur\u00edcio, A.C. (2022). Peripheral Nerve Injury Treatments and Advances: One Health Perspective. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020918"},{"key":"ref_4","unstructured":"Giuffre, B.A., Black, A.C., and Jeanmonod, R. (2026, February 19). Anatomy, Sciatic Nerve, Available online: https:\/\/www.ncbi.nlm.nih.gov\/sites\/books\/NBK482431\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/joa.13544","article-title":"The structure of sensory afferent compartments in health and disease","volume":"241","author":"Middleton","year":"2022","journal-title":"J. Anat."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Haberberger, R.V., Barry, C., Dominguez, N., and Matusica, D. (2019). Human Dorsal Root Ganglia. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00271"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00441-023-03770-w","article-title":"Ultrastructure of dorsal root ganglia","volume":"393","author":"Haberberger","year":"2023","journal-title":"Cell Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/ALN.0000000000004092","article-title":"Molecular Changes in the Dorsal Root Ganglion during the Late Phase of Peripheral Nerve Injury\u2013induced Pain in Rodents: A Systematic Review","volume":"136","author":"Chalaki","year":"2022","journal-title":"Anesthesiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gu, D., Xia, Y., Ding, Z., Qian, J., Gu, X., Bai, H., Jiang, M., and Yao, D. (2024). Inflammation in the Peripheral Nervous System after Injury. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061256"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e68457","DOI":"10.7554\/eLife.68457","article-title":"Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair","volume":"10","author":"Avraham","year":"2021","journal-title":"elife"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gordon, T. (2020). Peripheral Nerve Regeneration and Muscle Reinnervation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228652"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4103\/1673-5374.265540","article-title":"Peripheral nerve injury induced changes in the spinal cord and strategies to counteract\/enhance the changes to promote nerve regeneration","volume":"15","author":"Liu","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"884","DOI":"10.3390\/ani14060884","article-title":"Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury-State of the Art","volume":"14","author":"Gouveia","year":"2024","journal-title":"Animals"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116","DOI":"10.7150\/ijbs.35653","article-title":"Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery","volume":"16","author":"Hussain","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E3","DOI":"10.3171\/FOC.2009.26.2.E3","article-title":"The role of neurotrophic factors in nerve regeneration","volume":"26","author":"Gordon","year":"2009","journal-title":"Neurosurg. Focus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"493","DOI":"10.5603\/fm.102401","article-title":"Unveiling significance of peripheral nervous system glia: Implications for nervous system disorders and therapeutic interventions","volume":"84","author":"Wawrzyniak","year":"2025","journal-title":"Folia Morphol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1523\/JNEUROSCI.21-13-04891.2001","article-title":"Brain-Derived Neurotrophic Factor Increases in the Uninjured Dorsal Root Ganglion Neurons in Selective Spinal Nerve Ligation Model","volume":"21","author":"Fukuoka","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Klimovich, P., Rubina, K., Sysoeva, V., and Semina, E. (2020). Three-Dimensional Model of Dorsal Root Ganglion Explant as a Method of Studying Neurotrophic Factors in Regenerative Medicine. Biomedicines, 8.","DOI":"10.3390\/biomedicines8030049"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mashanov, V., Alwan, A., Kim, M.W., Lai, D., Poerio, A., Ju, Y.M., Kim, J.H., and Yoo, J.J. (2020). Synergistic effect of CNTF and GDNF on directed neurite growth in chick embryo dorsal root ganglia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240235"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bol\u00edvar, S., Navarro, X., and Udina, E. (2020). Schwann Cell Role in Selectivity of Nerve Regeneration. Cells, 9.","DOI":"10.3390\/cells9092131"},{"key":"ref_21","first-page":"981","article-title":"Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)","volume":"22","year":"2009","journal-title":"Oncol. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1111\/j.1742-4658.2008.06677.x","article-title":"Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues","volume":"275","author":"Cheung","year":"2008","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.anireprosci.2005.05.004","article-title":"Pituitary gonadotropin-releasing hormone (GnRH) receptor: Structure, distribution and regulation of expression","volume":"88","author":"Rispoli","year":"2005","journal-title":"Anim. Reprod. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, H.Q., Zhang, W.D., Yuan, B., and Zhang, J.B. (2021). Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion. Animals, 11.","DOI":"10.3390\/ani11041134"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Barab\u00e1s, K., Szab\u00f3-Meleg, E., and \u00c1brah\u00e1m, I.M. (2020). Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020529"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fanis, P., Neocleous, V., Papapetrou, I., Phylactou, L.A., and Skordis, N. (2023). Gonadotropin-Releasing Hormone Receptor (GnRHR) and Hypogonadotropic Hypogonadism. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115965"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"bqaf033","DOI":"10.1210\/endocr\/bqaf033","article-title":"GnRH and Cognition","volume":"166","author":"Kacimi","year":"2025","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105230","DOI":"10.1016\/j.yhbeh.2022.105230","article-title":"The roles of GnRH in the human central nervous system","volume":"145","author":"Wickramasuriya","year":"2022","journal-title":"Horm. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3390\/ijms22010114","article-title":"Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH, Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions","volume":"22","author":"Zakharova","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1159\/000545129","article-title":"Neurotrophic Effects of GH and GnRH in a Full Sciatic Nerve Transection Model in Male Rats","volume":"115","author":"Epardo","year":"2025","journal-title":"Neuroendocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Moreno, C.G., Calder\u00f3n-Vallejo, D., D\u00edaz-Galindo, C., Hern\u00e1ndez-Jasso, I., Olivares-Hern\u00e1ndez, J.D., \u00c1vila-Mendoza, J., Epardo, D., Balderas-M\u00e1rquez, J.E., Urban-Sosa, V.A., and Baltazar-Lara, R. (2023). Gonadotropin-releasing hormone and growth hormone act as anti-inflammatory factors improving sensory recovery in female rats with thoracic spinal cord injury. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1164044"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1517\/13543784.16.11.1851","article-title":"Leuprolide acetate: A drug of diverse clinical applications","volume":"16","author":"Wilson","year":"2007","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.4103\/1673-5374.170311","article-title":"Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats","volume":"10","author":"Galindo","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1007\/s11064-012-0842-x","article-title":"Leuprolide acetate, a GnRH agonist, improves experimental autoimmune encephalomyelitis: A possible therapy for multiple sclerosis","volume":"37","author":"Salinas","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"135439","DOI":"10.1016\/j.neulet.2020.135439","article-title":"Recovery of sciatic nerve with complete transection in rats treated with leuprolide acetate: A gonadotropin-releasing hormone agonist","volume":"739","author":"Quintanar","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"352","DOI":"10.21307\/ane-2018-034","article-title":"Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH","volume":"78","author":"Quintanar","year":"2018","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1179\/1476830513Y.0000000104","article-title":"Commiphora mukul attenuates peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats","volume":"18","author":"Mehta","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12311-008-0038-8","article-title":"The Gonadotropin-Releasing Hormone Type I Receptor is Expressed in the Mouse Cerebellum","volume":"7","author":"Albertson","year":"2008","journal-title":"Cerebellum"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jchemneu.2008.03.004","article-title":"Immunoreactive GnRH type I receptors in the mouse and sheep brain","volume":"35","author":"Albertson","year":"2008","journal-title":"J. Chem. Neuroanat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11064-020-03178-w","article-title":"Gonadotropin-Releasing Hormone Receptor Expression in Human Spinal Cord","volume":"46","author":"Quintanar","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0304-3940(03)00594-9","article-title":"Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor in sheep spinal cord","volume":"346","author":"Dolan","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_43","first-page":"475","article-title":"Brain gonadotropin releasing hormone receptors: Localization and regulation","volume":"52","author":"Jennes","year":"1997","journal-title":"Recent Prog. Horm. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Moreno, C.G., Calder\u00f3n-Vallejo, D., Harvey, S., Ar\u00e1mburo, C., and Quintanar, J.L. (2018). Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020375"},{"key":"ref_45","first-page":"43","article-title":"Modulation of M current in frog sympathetic ganglion cells","volume":"45","author":"Bosma","year":"1990","journal-title":"Soc. Gen. Physiol. Ser."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1152\/jn.00966.2007","article-title":"Differential neurotrophic regulation of sodium and calcium channels in an adult sympathetic neuron","volume":"99","author":"Ford","year":"2008","journal-title":"J. Neurophysiol."},{"key":"ref_47","first-page":"104","article-title":"The effect of short-term treatments of a gonadotropin-releasing hormone analog (buserelin) on sciatic nerve regeneration","volume":"15","author":"Farjah","year":"2014","journal-title":"Iran. J. Vet. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26420","DOI":"10.1038\/s41598-024-78073-3","article-title":"Neurotrophic and synaptic effects of GnRH and\/or GH upon motor function after spinal cord injury in rats","volume":"14","author":"Epardo","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/neu.20081","article-title":"Temperature perception and nociception","volume":"61","author":"Green","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.celrep.2018.04.065","article-title":"Sensory Afferents Use Different Coding Strategies for Heat and Cold","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuroscience.2017.10.037","article-title":"Signaling Pathways Relevant to Nerve Growth Factor-induced Upregulation of Transient Receptor Potential M8 Expression","volume":"367","author":"Kayama","year":"2017","journal-title":"Neuroscience"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S0197-4580(02)00234-8","article-title":"Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats","volume":"24","author":"Azcoitia","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_53","first-page":"33","article-title":"Clinical development of the GnRH agonist leuprolide acetate depot","volume":"4","author":"Chwalisz","year":"2022","journal-title":"FS Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"156","DOI":"10.12688\/wellcomeopenres.17885.1","article-title":"Comparative transcriptional analysis of satellite glial cell injury response","volume":"7","author":"Jager","year":"2022","journal-title":"Wellcome Open Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.neuron.2014.10.019","article-title":"Axonal transport: Cargo-specific mechanisms of motility and regulation","volume":"84","author":"Maday","year":"2014","journal-title":"Neuron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5965","DOI":"10.1523\/JNEUROSCI.4680-13.2014","article-title":"CNS axons globally increase axonal transport after peripheral conditioning","volume":"34","author":"Mar","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.tins.2010.03.006","article-title":"Retrograde Axonal Transport: Pathways To Cell Death?","volume":"33","author":"Perlson","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/dneu.22608","article-title":"The Virtuous Cycle of Axon Growth: Axonal Transport of Growth-Promoting Machinery as an Intrinsic Determinant of Axon Regeneration","volume":"78","author":"Petrova","year":"2018","journal-title":"Dev. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/emboj.2011.494","article-title":"Axonal transcription factors signal retrogradely in lesioned peripheral nerve","volume":"31","author":"Dagan","year":"2012","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0361-9230(87)90161-4","article-title":"Retrograde axonal transport in rat sciatic nerve after nerve crush injury","volume":"19","author":"Fink","year":"1987","journal-title":"Brain Res. Bull."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1113\/JP270874","article-title":"The repair Schwann cell and its function in regenerating nerves","volume":"594","author":"Jessen","year":"2016","journal-title":"J. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Konnova, E.A., Deftu, A.F., Chu Sin Chung, P., Pertin, M., Kirschmann, G., Decosterd, I., and Suter, M.R. (2023). Characterisation of GFAP-Expressing Glial Cells in the Dorsal Root Ganglion after Spared Nerve Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115559"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1097\/BRS.0b013e3181ab1f68","article-title":"The Effects of Inflammation on Glial Fibrillary Acidic Protein Expression in Satellite Cells of the Dorsal Root Ganglion","volume":"34","author":"Siemionow","year":"2009","journal-title":"Spine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.pain.2009.02.006","article-title":"Profiling of dynamically changed gene expression in dorsal root ganglia post peripheral nerve injury and a critical role of injury-induced glial fibrillary acetic protein in maintenance of pain behaviors","volume":"143","author":"Kim","year":"2009","journal-title":"Pain"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gheorghe, R.O., Grosu, A.V., Magercu, M., Ghenghea, M.S., Zbarcea, C.E., Tanase, A., Negres, S., Filippi, A., Chiritoiu, G., and Gherghiceanu, M. (2023). Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115831"},{"key":"ref_66","first-page":"E1137","article-title":"Exercise Facilitates the M1-to-M2 Polarization of Microglia by Enhancing Autophagy via the BDNF\/AKT\/mTOR Pathway in Neuropathic Pain","volume":"25","author":"Bai","year":"2022","journal-title":"Pain Physician"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bbi.2016.05.021","article-title":"Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain","volume":"58","author":"Li","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41467-019-13839-2","article-title":"Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain","volume":"11","author":"Yu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000438927","article-title":"Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-\u03baB Activation","volume":"23","author":"Salinas","year":"2016","journal-title":"Neuroimmunomodulation"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/nau.23505","article-title":"Administration of leuprolide acetate, a GnRH agonist, improves urodynamic parameters in ovariectomized rats","volume":"37","author":"Munoz","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"ref_71","first-page":"83","article-title":"Analysis of hippocampus in rats with acute brain ischemia-reperfusion injury treated with leuprolide acetate, an agonist of GnRH","volume":"41","author":"Quintanar","year":"2023","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000533388","article-title":"Effect of leuprolide acetate, a GnRH agonist, on neuroinflammation and anxiety-like behavior after mild hypoxic-ischemic encephalopathy in rat model","volume":"30","author":"Salinas","year":"2023","journal-title":"Neuroimmunomodulation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16888","DOI":"10.1038\/srep16888","article-title":"The transcriptional landscape of dorsal root ganglia after sciatic nerve transection","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1073\/pnas.1015239108","article-title":"In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration","volume":"108","author":"Bareyre","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.bbrc.2010.03.092","article-title":"Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells","volume":"394","author":"Cao","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12974-019-1421-8","article-title":"TNF-\u03b1\/STAT3 pathway epigenetically upregulates Nav1.6 expression in DRG and contributes to neuropathic pain induced by L5-VRT","volume":"16","author":"Ding","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1471-4159.2008.05566.x","article-title":"JAK\/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat","volume":"107","author":"Dominguez","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/intimm\/dxr077","article-title":"IL-1\u03b2 and TNF\u03b1-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis","volume":"23","author":"Mori","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awr025","article-title":"JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats","volume":"134","author":"Tsuda","year":"2011","journal-title":"Brain"},{"key":"ref_80","first-page":"1","article-title":"Therapeutic approaches of trophic factors in animal models and in patients with spinal cord injury","volume":"38","author":"Quintanar","year":"2020","journal-title":"Growth Factors"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9512","DOI":"10.1523\/JNEUROSCI.2160-06.2006","article-title":"Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons","volume":"26","author":"Miao","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature10594","article-title":"Sustained axon regeneration induced by co-deletion of PTEN and SOCS3","volume":"480","author":"Sun","year":"2011","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"107657","DOI":"10.1016\/j.celrep.2020.107657","article-title":"CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia","volume":"31","author":"Hu","year":"2020","journal-title":"Cell Reports"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1046\/j.1460-9568.2000.00005.x","article-title":"Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT)","volume":"12","author":"Schwaiger","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1523\/JNEUROSCI.3481-16.2017","article-title":"STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration","volume":"37","author":"Benito","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/pm\/pny159","article-title":"Activation of the RAGE\/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation","volume":"20","author":"Zhang","year":"2017","journal-title":"Pain Physician"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/jnc.14998","article-title":"Down-regulation of microRNA-34c-5p alleviates neuropathic pain via the SIRT1\/STAT3 signaling pathway in rat models of chronic constriction injury of sciatic nerve","volume":"154","author":"Mo","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/jnr.490420314","article-title":"Comparison of c-jun, junB, and junD mRNA expression and protein in the rat dorsal root ganglia following sciatic nerve transection","volume":"42","author":"Nahin","year":"1995","journal-title":"J. Neurosci. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/j.1460-9568.1993.tb00539.x","article-title":"Expression of c-Jun as a response to dorsal root and peripheral nerve section in damaged and adjacent intact primary sensory neurons in the rat","volume":"5","author":"Jenkins","year":"1993","journal-title":"Eur. J. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1006\/exnr.1997.6665","article-title":"c-Jun expression in adult rat dorsal root ganglion neurons: Differential response after central or peripheral axotomy","volume":"148","author":"Broude","year":"1997","journal-title":"Exp. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0306-4522(93)90111-R","article-title":"Expression of immediate early gene proteins following axotomy and inhibition of axonal transport in the rat central nervous system","volume":"57","author":"Leah","year":"1993","journal-title":"Neuroscience"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molbrainres.2005.01.008","article-title":"Early changes in gene expression in the dorsal root ganglia after transection of the sciatic nerve; effects of amphiregulin and PAI-1 on regeneration","volume":"136","author":"Nilsson","year":"2005","journal-title":"Mol. Brain Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/exnr.2000.7558","article-title":"Differential and prolonged expression of Fos-lacZ and Jun-lacZ in neurons, glia, and muscle following sciatic nerve damage","volume":"167","author":"Soares","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/pros.2990130204","article-title":"Calcium channel antagonists delay regression of androgen-dependent tissues and suppress gene activity associated with cell death","volume":"13","author":"Connor","year":"1988","journal-title":"Prostate"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"530","DOI":"10.4103\/0028-3886.68665","article-title":"Protective effects of the calcium-channel blocker flunarizine on crush injury of sciatic nerves in a rat model","volume":"58","author":"Su","year":"2010","journal-title":"Neurol. India"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1038\/s41467-021-21731-1","article-title":"ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking","volume":"12","author":"Xie","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9316","DOI":"10.1523\/JNEUROSCI.0648-19.2019","article-title":"The Cofilin\/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor Axons","volume":"39","author":"Frendo","year":"2019","journal-title":"J. Neurosci."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/3\/332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:20:05Z","timestamp":1774610405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/3\/332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":97,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["brainsci16030332"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16030332","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}