{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:01:26Z","timestamp":1793347286902,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["J230008"],"award-info":[{"award-number":["J230008"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["2023YFC2410605"],"award-info":[{"award-number":["2023YFC2410605"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["82401612"],"award-info":[{"award-number":["82401612"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&amp;D Program of China","award":["J230008"],"award-info":[{"award-number":["J230008"]}]},{"name":"National Key R&amp;D Program of China","award":["2023YFC2410605"],"award-info":[{"award-number":["2023YFC2410605"]}]},{"name":"National Key R&amp;D Program of China","award":["82401612"],"award-info":[{"award-number":["82401612"]}]},{"name":"National Natural Science Foundation of China","award":["J230008"],"award-info":[{"award-number":["J230008"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFC2410605"],"award-info":[{"award-number":["2023YFC2410605"]}]},{"name":"National Natural Science Foundation of China","award":["82401612"],"award-info":[{"award-number":["82401612"]}]},{"name":"Beijing Neurosurgical Institute","award":["J230008"],"award-info":[{"award-number":["J230008"]}]},{"name":"Beijing Neurosurgical Institute","award":["2023YFC2410605"],"award-info":[{"award-number":["2023YFC2410605"]}]},{"name":"Beijing Neurosurgical Institute","award":["82401612"],"award-info":[{"award-number":["82401612"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-\u03baB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-\u03baB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function.<\/jats:p>","DOI":"10.3390\/brainsci15080837","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:33:06Z","timestamp":1754555586000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Contralateral Structure and Molecular Response to Severe Unilateral Brain Injury"],"prefix":"10.3390","volume":"15","author":[{"given":"Xixian","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojian","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runfa","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8907-9357","authenticated-orcid":false,"given":"Yuan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mcna.2019.11.001","article-title":"Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and Medical Management","volume":"104","author":"Capizzi","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1111\/joim.12900","article-title":"Treatments and rehabilitation in the acute and chronic state of traumatic brain injury","volume":"285","author":"Marklund","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1007\/s12031-021-01841-7","article-title":"Traumatic Brain Injury: Mechanistic Insight on Pathophysiology and Potential Therapeutic Targets","volume":"71","author":"Thapa","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12974-024-03167-8","article-title":"Inflammasomes at the crossroads of traumatic brain injury and post-traumatic epilepsy","volume":"21","author":"Javalgekar","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ncl.2024.08.002","article-title":"Neuroworsening in Moderate Traumatic Brain Injury","volume":"43","author":"Godoy","year":"2025","journal-title":"Neurol. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mira, R.G., Lira, M., and Cerpa, W. (2021). Traumatic Brain Injury: Mechanisms of Glial Response. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.740939"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/brain\/awaa321","article-title":"The synapse in traumatic brain injury","volume":"144","author":"Jamjoom","year":"2021","journal-title":"Brain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1111\/bph.15488","article-title":"TLR4 pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury","volume":"178","author":"Rosa","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neuron.2014.01.043","article-title":"Microglial CR3 activation triggers long-term synaptic depression in the hippocampus via NADPH oxidase","volume":"82","author":"Zhang","year":"2014","journal-title":"Neuron"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Krukowski, K., Chou, A., Feng, X., Tiret, B., Paladini, M.S., Riparip, L.K., Chaumeil, M.M., Lemere, C., and Rosi, S. (2018). Traumatic Brain Injury in Aged Mice Induces Chronic Microglia Activation, Synapse Loss, and Complement-Dependent Memory Deficits. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123753"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1172\/JCI92300","article-title":"Enhanced astrocytic d-serine underlies synaptic damage after traumatic brain injury","volume":"127","author":"Perez","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1759091416630220","DOI":"10.1177\/1759091416630220","article-title":"Astrocytic Ephrin-B1 Regulates Synapse Remodeling Following Traumatic Brain Injury","volume":"8","author":"Nikolakopoulou","year":"2016","journal-title":"ASN Neuro"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shu, H., Parada, I., Delgado, A., Prince, D.A., and Gu, F. (2024). Increased excitatory connectivity and epileptiform activity in thrombospondin1\/2 knockout mice following cortical trauma. Neurobiol. Dis., 200.","DOI":"10.1016\/j.nbd.2024.106634"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1523\/JNEUROSCI.1930-15.2016","article-title":"Blockade of Astrocytic Calcineurin\/NFAT Signaling Helps to Normalize Hippocampal Synaptic Function and Plasticity in a Rat Model of Traumatic Brain Injury","volume":"36","author":"Furman","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_16","first-page":"73","article-title":"Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat","volume":"31","author":"Axelson","year":"2013","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"ENEURO.0548-20.2021","DOI":"10.1523\/ENEURO.0548-20.2021","article-title":"Left-Right Side-Specific Neuropeptide Mechanism Mediates Contralateral Responses to a Unilateral Brain Injury","volume":"8","author":"Watanabe","year":"2021","journal-title":"Eneuro"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1038\/s41467-022-29992-0","article-title":"Selective plasticity of callosal neurons in the adult contralesional cortex following murine traumatic brain injury","volume":"13","author":"Empl","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.brainresbull.2022.07.010","article-title":"Contralateral synaptic changes following severe unilateral brain injury","volume":"188","author":"Zhuang","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1002\/cpns.69","article-title":"Golgi-Cox Staining of Neuronal Dendrites and Dendritic Spines with FD Rapid GolgiStain\u2122 Kit","volume":"88","author":"Du","year":"2019","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1111\/cns.14223","article-title":"Megf10-related engulfment of excitatory postsynapses by astrocytes following severe brain injury","volume":"29","author":"Zhuang","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.semcdb.2018.07.019","article-title":"Modulating transcription factor activity: Interfering with protein-protein interaction networks","volume":"99","author":"Francois","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.freeradbiomed.2021.11.011","article-title":"Spatial transcriptome analysis defines heme as a hemopexin-targetable inflammatoxin in the brain","volume":"179","author":"Buzzi","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s40478-018-0569-2","article-title":"ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms","volume":"6","author":"Castranio","year":"2018","journal-title":"Acta. Neuropathol. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"140796","DOI":"10.1016\/j.scitotenv.2020.140796","article-title":"Transcriptome analysis reveals the mechanism of common carp brain injury after exposure to lead","volume":"743","author":"Zhang","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1038\/s41467-025-59856-2","article-title":"Single-nucleus and spatial signatures of the brainstem in normal brain and mild traumatic brain injury in male mice","volume":"16","author":"Zhuang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41419-019-1777-9","article-title":"Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke","volume":"10","author":"Xu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/cns.13256","article-title":"Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain","volume":"25","author":"Zhang","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12974-021-02197-w","article-title":"Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response","volume":"18","author":"Todd","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s40478-021-01226-2","article-title":"Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: A transcriptomic study","volume":"9","author":"Toutonji","year":"2021","journal-title":"Acta. Neuropathol. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6943","DOI":"10.1038\/s41467-021-27248-x","article-title":"Stroke subtype-dependent synapse elimination by reactive gliosis in mice","volume":"12","author":"Shi","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chung, W.S., Baldwin, K.T., and Allen, N.J. (2024). Astrocyte Regulation of Synapse Formation, Maturation, and Elimination. Cold Spring Harb. Perspect. Biol., 16.","DOI":"10.1101\/cshperspect.a041352"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Smith, A.M., Taylor, E.B., Brooks, R.J., Dos Santos, E.S.C., and Grayson, B.E. (2024). Cerebral and Peripheral Immune Cell Changes following Rodent Juvenile Traumatic Brain Injury. Brain Sci., 14.","DOI":"10.3390\/brainsci14040398"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.1523\/JNEUROSCI.1644-21.2022","article-title":"Microglial Tmem59 Deficiency Impairs Phagocytosis of Synapse and Leads to Autism-Like Behaviors in Mice","volume":"42","author":"Meng","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"White, T.E., Ford, G.D., Surles-Zeigler, M.C., Gates, A.S., Laplaca, M.C., and Ford, B.D. (2013). Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-282"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1161\/STROKEAHA.120.029440","article-title":"Sustained Increases in Immune Transcripts and Immune Cell Trafficking During the Recovery of Experimental Brain Ischemia","volume":"51","author":"Fury","year":"2020","journal-title":"Stroke"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gpb.2019.09.006","article-title":"hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets","volume":"18","author":"Zhang","year":"2020","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1534\/genetics.120.303776","article-title":"Survival Following Traumatic Brain Injury in Drosophila Is Increased by Heterozygosity for a Mutation of the NF-\u03baB Innate Immune Response Transcription Factor Relish","volume":"216","author":"Swanson","year":"2020","journal-title":"Genetics"},{"key":"ref_39","first-page":"3203","article-title":"Biphasic activation of nuclear factor-\u03baB and expression of p65 and c-Rel following traumatic neuronal injury","volume":"41","author":"Zhang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.2174\/1570159X18666200522203542","article-title":"Transcriptional Factors and Protein Biomarkers as Target Therapeutics in Traumatic Spinal Cord and Brain Injury","volume":"18","author":"Kumar","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1093\/cercor\/bhx164","article-title":"Inhibition of c-Jun N-Terminal Kinase Protects Against Brain Damage and Improves Learning and Memory After Traumatic Brain Injury in Adult Mice","volume":"28","author":"Rehman","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1002\/jcp.29183","article-title":"JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke","volume":"235","author":"Zheng","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cheng, H., Men, Y., An, Y., Yu, J., Zhang, G., Li, J., Wang, X., Sun, G., and Wu, Y. (2024). Overexpression of endothelial S1pr2 promotes blood-brain barrier disruption via JNK\/c-Jun\/MMP-9 pathway after traumatic brain injury in both in vivo and in vitro models. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1448570"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.4103\/NRR.NRR-D-23-01772","article-title":"High-dose dexamethasone regulates microglial polarization via the GR\/JAK1\/STAT3 signaling pathway after traumatic brain injury","volume":"20","author":"Yang","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1038\/ncomms5294","article-title":"Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression","volume":"5","author":"Tyzack","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8480","DOI":"10.7150\/thno.60031","article-title":"Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-\u03b2 signaling","volume":"11","author":"Wu","year":"2021","journal-title":"Theranostics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108829","DOI":"10.1016\/j.celrep.2021.108829","article-title":"Astrocyte-derived small extracellular vesicles promote synapse formation via fibulin-2-mediated TGF-\u03b2 signaling","volume":"34","author":"Patel","year":"2021","journal-title":"Cell Rep."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/8\/837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:23:12Z","timestamp":1760034192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/8\/837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["brainsci15080837"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15080837","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,5]]}}}