{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:05:21Z","timestamp":1780639521419,"version":"3.54.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint key project","award":["2019LH01"],"award-info":[{"award-number":["2019LH01"]}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["22CXRC0178"],"award-info":[{"award-number":["22CXRC0178"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018610","name":"Innovation Program in Military Medicine of Chinese People\u2019s Liberation Army","doi-asserted-by":"publisher","award":["21WQ040"],"award-info":[{"award-number":["21WQ040"]}],"id":[{"id":"10.13039\/501100018610","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Southwest Jiaotong University Medical and industrial Combination training special project","award":["2682021ZTPY024"],"award-info":[{"award-number":["2682021ZTPY024"]}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701283"],"award-info":[{"award-number":["81701283"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hospital Management Project of Western Command General Hospital","award":["2021-XZYG-B22"],"award-info":[{"award-number":["2021-XZYG-B22"]}]},{"name":"Hospital Management Project of Western Command General Hospital","award":["2021-XZYG-B21"],"award-info":[{"award-number":["2021-XZYG-B21"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The recovery process from traumatic brain injury (TBI) is significantly impeded by inhibitors such as Nogo-A, myelin associated glycoprotein, and oligodendrocyte myelin glycoprotein, which exert an impact on the regeneration and repair of neuronal axons through their binding to Nogo-66 receptor 1 (NgR1). Recent research findings have revealed that NgR1 signaling may play a pivotal role in various seizure mechanisms, including the regulation of synaptic plasticity and migration of neural precursor cells. In this study, wild type (WT) and NgR1 knockout (KO) mice were utilized to establish craniocerebral injury models, while pentylenetetrazol (PTZ) was employed to induce seizures in both groups of mice following TBI. The results revealed that NgR1 KO mice exhibited heightened levels of neuronal electrical activity, along with elevated seizure scores compared to WT controls. Immunofluorescence staining demonstrated an increase in the number of excitatory synapses (P &lt;\u2009 0.001) and a decrease in inhibitory synaptic density (P &lt;\u2009 0.001) in NgR1 KO mice. Furthermore, the NgR1 KO model mice also displayed an augmentation in the number of presynaptic vesicles (P &lt;\u2009 0.001), a narrowing of the synaptic gap (P &lt;\u2009 0.001), and an elongation of the synaptic active region (P &lt;\u2009 0.001). Our findings have demonstrated that in the previous single cognition of NgR1 inhibition in nerve function repair following TBI, revealing the potential risks associated with inhibiting NgR1 activity in nerve function repair following TBI, and providing a new perspective for understanding the role of NgR1 in the nervous system.<\/jats:p>","DOI":"10.1371\/journal.pone.0321447","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T17:23:41Z","timestamp":1744737821000},"page":"e0321447","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["NgR1 knockout increased neuronal excitability and altered seizure pattern in traumatic brain injury mice brain after PTZ-induced seizure"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-2651","authenticated-orcid":true,"given":"Jinwei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejun","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqin","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"pone.0321447.ref001","doi-asserted-by":"crossref","first-page":"1147194","DOI":"10.3389\/fnins.2023.1147194","article-title":"Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis","volume":"17","author":"Z-L Yang","year":"2023","journal-title":"Front Neurosci"},{"issue":"8","key":"pone.0321447.ref002","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrn1956","article-title":"Glial inhibition of CNS axon regeneration","volume":"7","author":"G Yiu","year":"2006","journal-title":"Nat Rev Neurosci"},{"issue":"7","key":"pone.0321447.ref003","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1089\/neu.2018.5949","article-title":"Role of Nogo Receptor-1 for Recovery of Balance, Cognition, and Emotion after Mild Traumatic Brain Injury in Mice","volume":"36","author":"J-H Lai","year":"2019","journal-title":"J Neurotrauma"},{"issue":"6888","key":"pone.0321447.ref004","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/417547a","article-title":"Nogo-66 receptor antagonist peptide promotes axonal regeneration","volume":"417","author":"T GrandPr\u00e9","year":"2002","journal-title":"Nature"},{"issue":"1","key":"pone.0321447.ref005","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1227\/NEU.0000000000000337","article-title":"Assessment of Nogo-66 receptor 1 function in vivo after spinal cord injury","volume":"75","author":"J Tong","year":"2014","journal-title":"Neurosurgery"},{"issue":"1","key":"pone.0321447.ref006","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13195-020-00616-3","article-title":"Reduction of NgR in perforant path decreases amyloid-\u03b2 peptide production and ameliorates synaptic and cognitive deficits in APP\/PS1 mice","volume":"12","author":"R Jiang","year":"2020","journal-title":"Alzheimers Res Ther"},{"issue":"10","key":"pone.0321447.ref007","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.4103\/1673-5374.257531","article-title":"Soluble Nogo receptor 1 fusion protein protects neural progenitor cells in rats with ischemic stroke","volume":"14","author":"H-W He","year":"2019","journal-title":"Neural Regen Res"},{"issue":"5744","key":"pone.0321447.ref008","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1126\/science.1114362","article-title":"Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor","volume":"309","author":"AW McGee","year":"2005","journal-title":"Science"},{"issue":"Pt 6","key":"pone.0321447.ref009","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1093\/brain\/aws100","article-title":"Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation","volume":"135","author":"S Petratos","year":"2012","journal-title":"Brain"},{"issue":"37","key":"pone.0321447.ref010","doi-asserted-by":"crossref","first-page":"12432","DOI":"10.1523\/JNEUROSCI.0895-10.2010","article-title":"Oligodendrocyte-myelin glycoprotein and Nogo negatively regulate activity-dependent synaptic plasticity","volume":"30","author":"SJ Raiker","year":"2010","journal-title":"J Neurosci"},{"issue":"11","key":"pone.0321447.ref011","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1523\/JNEUROSCI.5586-07.2008","article-title":"Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength","volume":"28","author":"H Lee","year":"2008","journal-title":"J Neurosci"},{"issue":"5","key":"pone.0321447.ref012","first-page":"2779","article-title":"Nogo-66 Restricts Synaptic Strengthening via Lingo1 and the ROCK2-Cofilin Pathway to Control Actin Dynamics","volume":"27","author":"C Iobbi","year":"2017","journal-title":"Cereb Cortex"},{"issue":"16","key":"pone.0321447.ref013","doi-asserted-by":"crossref","first-page":"6583","DOI":"10.1073\/pnas.1217665110","article-title":"Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function","volume":"110","author":"B Tews","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0321447.ref014","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.conb.2014.02.011","article-title":"Nogo limits neural plasticity and recovery from injury","volume":"27","author":"ME Schwab","year":"2014","journal-title":"Curr Opin Neurobiol"},{"key":"pone.0321447.ref015","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fncel.2020.00227","article-title":"That\u2019s a Wrap! Molecular Drivers Governing Neuronal Nogo Receptor-Dependent Myelin Plasticity and Integrity","volume":"14","author":"S Petratos","year":"2020","journal-title":"Front Cell Neurosci"},{"issue":"4","key":"pone.0321447.ref016","doi-asserted-by":"crossref","first-page":"ENEURO.0185-18.2018","DOI":"10.1523\/ENEURO.0185-18.2018","article-title":"The Nogo Receptor Ligand LGI1 Regulates Synapse Number and Synaptic Activity in Hippocampal and Cortical Neurons","volume":"5","author":"RA Thomas","year":"2018","journal-title":"eNeuro"},{"issue":"1","key":"pone.0321447.ref017","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ejpn.2016.07.007","article-title":"Cerebral plasticity: Windows of opportunity in the developing brain","volume":"21","author":"FY Ismail","year":"2017","journal-title":"Eur J Paediatr Neurol"},{"issue":"6","key":"pone.0321447.ref018","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1111\/j.1471-4159.2011.07520.x","article-title":"Neuronal Nogo-A regulates glutamate receptor subunit expression in hippocampal neurons","volume":"119","author":"X Peng","year":"2011","journal-title":"J Neurochem"},{"issue":"3","key":"pone.0321447.ref019","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00441-002-0695-8","article-title":"Activity-induced and developmental downregulation of the Nogo receptor","volume":"311","author":"A Josephson","year":"2003","journal-title":"Cell Tissue Res"},{"issue":"21","key":"pone.0321447.ref020","first-page":"4516","article-title":"The relationship between the occurrence of intractable epilepsy with glial cells and myelin sheath - an experimental study","volume":"20","author":"X Hu","year":"2016","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"2","key":"pone.0321447.ref021","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/neu.1995.12.169","article-title":"A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects","volume":"12","author":"DH Smith","year":"1995","journal-title":"J Neurotrauma"},{"issue":"4","key":"pone.0321447.ref022","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/cns.13069","article-title":"Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice","volume":"25","author":"B-S Xie","year":"2019","journal-title":"CNS Neurosci Ther"},{"key":"pone.0321447.ref023","doi-asserted-by":"crossref","first-page":"9.52.1-9.52.16","DOI":"10.1002\/cpns.10","article-title":"The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents","volume":"75","author":"AM Yarnell","year":"2016","journal-title":"Curr Protoc Neurosci"},{"issue":"6","key":"pone.0321447.ref024","doi-asserted-by":"crossref","first-page":"e0158231","DOI":"10.1371\/journal.pone.0158231","article-title":"Chronic Posttraumatic Epilepsy following Neocortical Undercut Lesion in Mice","volume":"11","author":"X Ping","year":"2016","journal-title":"PLoS One"},{"issue":"136","key":"pone.0321447.ref025","first-page":"56573","article-title":"Pentylenetetrazole-Induced Kindling Mouse Model","author":"T Shimada","year":"2018","journal-title":"J Vis Exp"},{"key":"pone.0321447.ref026","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.yebeh.2018.09.016","article-title":"Automated quantification of EEG spikes and spike clusters as a new read out in Theiler\u2019s virus mouse model of encephalitis-induced epilepsy","volume":"88","author":"SMM Anjum","year":"2018","journal-title":"Epilepsy Behav"},{"issue":"2","key":"pone.0321447.ref027","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/epi.13648","article-title":"TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice","volume":"58","author":"KD Phelan","year":"2017","journal-title":"Epilepsia"},{"issue":"7","key":"pone.0321447.ref028","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1111\/epi.16551","article-title":"Modulation of posttraumatic epileptogenesis in aquaporin-4 knockout mice","volume":"61","author":"JI Szu","year":"2020","journal-title":"Epilepsia"},{"key":"pone.0321447.ref029","first-page":"879716","article-title":"Brainstorm: a user-friendly application for MEG\/EEG analysis","author":"F Tadel","year":"2011","journal-title":"Comput Intell Neurosci"},{"issue":"45","key":"pone.0321447.ref030","first-page":"2270","article-title":"Quantifying synapses: an immunocytochemistry-based assay to quantify synapse number","author":"DM Ippolito","year":"2010","journal-title":"J Vis Exp"},{"key":"pone.0321447.ref031","doi-asserted-by":"crossref","first-page":"24428","DOI":"10.1038\/srep24428","article-title":"Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS","volume":"6","author":"B Yi","year":"2016","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0321447.ref032","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.neuron.2011.11.029","article-title":"The nogo receptor family restricts synapse number in the developing hippocampus","volume":"73","author":"ZP Wills","year":"2012","journal-title":"Neuron"},{"issue":"1","key":"pone.0321447.ref033","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/cercor\/bhv232","article-title":"Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery","volume":"26","author":"S Jitsuki","year":"2016","journal-title":"Cereb Cortex"},{"issue":"5544","key":"pone.0321447.ref034","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1126\/science.1067020","article-title":"The molecular biology of memory storage: a dialogue between genes and synapses","volume":"294","author":"ER Kandel","year":"2001","journal-title":"Science"},{"issue":"5","key":"pone.0321447.ref035","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1089\/neu.2011.1954","article-title":"Development of post-traumatic epilepsy after controlled cortical impact and lateral fluid-percussion-induced brain injury in the mouse","volume":"29","author":"T Bolkvadze","year":"2012","journal-title":"J Neurotrauma"},{"issue":"1","key":"pone.0321447.ref036","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/neu.2010.1383","article-title":"Post-traumatic seizures exacerbate histopathological damage after fluid-percussion brain injury","volume":"28","author":"Y Bao","year":"2011","journal-title":"J Neurotrauma"},{"issue":"11","key":"pone.0321447.ref037","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.4103\/1673-5374.282250","article-title":"Nogo-A and the regulation of neurotransmitter receptors","volume":"15","author":"BL Tang","year":"2020","journal-title":"Neural Regen Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T17:23:50Z","timestamp":1744737830000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0321447"}},"subtitle":[],"editor":[{"given":"Michael","family":"Massiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0321447","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]}}}