CX3CR1–TLR4 Axis as a Shared Neuroimmune Target in COVID-19 and Epilepsy: Integrative Transcriptomics and Gabapentin Repositioning

DOI record: { "DOI": "10.3390/biomedicines13092133", "ISSN": [ "2227-9059" ], "URL": "http://dx.doi.org/10.3390/biomedicines13092133", "abstract": "<jats:p>Introduction: Neuroinflammation is a common pathological hallmark of Coronavirus Disease 2019 (COVID-19) and epilepsy; however, their shared immunogenomic mechanisms remain poorly defined. This study explores shared immune-inflammatory transcriptomic signatures and identifies potential repositioning therapeutics. Methods: We integrated single-cell RNA-seq data from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and healthy donors (GSE149689), and bulk RNA-seq data from hippocampal tissue of patients with Temporal Lobe Epilepsy with Hippocampal Sclerosis (TLE-HS) and healthy controls (GSE256068). Common Differentially Expressed Genes (DEGs) were identified and subjected to GO/KEGG enrichment, a PPI network, hub gene detection (cytoHubba), and transcriptional regulation analysis (ENCODE-based TF/miRNA networks). Drug repositioning was performed using the LINCS L1000 database. Results: We identified 25 DEGs shared across datasets, including 22 upregulated genes enriched in cytokine–cytokine receptor interaction, NF-κB, and Toll-like receptor pathways. PPI analysis revealed a CX3CR1–TLR4-centered immune module. Gabapentin emerged as a promising repositioning candidate with potential to downregulate CX3CR1, TLR4, and selectin P ligand (SELPLG). Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of these targets (AUC &gt; 0.90 in epilepsy). A mechanistic model was proposed to illustrate Gabapentin’s dual action on microglial polarization and cytokine suppression. Conclusions: Our results reveal a shared CX3CR1–TLR4–NF-κB inflammatory axis in COVID-19 and epilepsy, supporting Gabapentin as a potential dual-action immunomodulator. These findings reveal a previously underappreciated immunomodulatory role for Gabapentin, providing mechanistic rationale for its repositioning in neuroinflammatory conditions beyond seizure control.</jats:p>", "alternative-id": [ "biomedicines13092133" ], "author": [ { "affiliation": [ { "name": "Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China" } ], "family": "Pan", "given": "Nannan", "sequence": "first" }, { "affiliation": [ { "name": "Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China" } ], "family": "Cao", "given": "Penghui", "sequence": "additional" }, { "affiliation": [ { "name": "Geriatric Neuroscience Center, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China" } ], "family": "Chen", "given": "Ben", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China" } ], "family": "Chen", "given": "Li", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China" } ], "family": "Liao", "given": "Xuezhen", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-5727-2782", "affiliation": [ { "name": "Geriatric Neuroscience Center, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China" }, { "name": "Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou 511436, China" } ], "authenticated-orcid": false, "family": "Ning", "given": "Yuping", "sequence": "additional" } ], "container-title": "Biomedicines", "container-title-short": "Biomedicines", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 9, 1 ] ], "date-time": "2025-09-01T13:27:44Z", "timestamp": 1756733264000 }, "deposited": { "date-parts": [ [ 2025, 9, 1 ] ], "date-time": "2025-09-01T13:59:01Z", "timestamp": 1756735141000 }, "funder": [ { "DOI": "10.13039/501100001809", "award": [ "82371428", "82171533" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100001809", "id-type": "DOI" } ], "name": "National Natural Science Foundation of China" }, { "DOI": "10.13039/501100003453", "award": [ "2022A1515011623", "2024A1515011035" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100003453", "id-type": "DOI" } ], "name": "Natural Science Foundation of Guangdong Province" }, { "award": [ "202201003" ], "name": "Science and Technology Program of Liwan District, Guangzhou" }, { "award": [ "2023A03J0852", "2023A03J0853", "2023A03J0850" ], "name": "Guangzhou Science and Technology Plan Project—University-Enterprise Joint Funding" }, { "award": [ "2021ZD0201800" ], "name": "National Brain Science and Brain-Like Intelligence Technology Project" } ], "indexed": { "date-parts": [ [ 2025, 9, 1 ] ], "date-time": "2025-09-01T14:40:01Z", "timestamp": 1756737601461, "version": "3.44.0" }, "is-referenced-by-count": 0, "issue": "9", "issued": { "date-parts": [ [ 2025, 8, 31 ] ] }, "journal-issue": { "issue": "9", "published-online": { "date-parts": [ [ 2025, 9 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 8, 31 ] ], "date-time": "2025-08-31T00:00:00Z", "timestamp": 1756598400000 } } ], "link": [ { "URL": "https://www.mdpi.com/2227-9059/13/9/2133/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "2133", "prefix": "10.3390", "published": { "date-parts": [ [ 2025, 8, 31 ] ] }, "published-online": { "date-parts": [ [ 2025, 8, 31 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1001/jama.2022.10594", "article-title": "Review of Antiseizure Medications for Adults With Epilepsy", "author": "Majeed", "doi-asserted-by": "crossref", "first-page": "680", "journal-title": "JAMA", "key": "ref_1", "volume": "328", "year": "2022" }, { "DOI": "10.1038/s41573-024-00981-w", "article-title": "New epilepsy therapies in development", "author": "Klein", "doi-asserted-by": "crossref", "first-page": "682", "journal-title": "Nat. Rev. Drug Discov.", "key": "ref_2", "volume": "23", "year": "2024" }, { "DOI": "10.1038/s41582-019-0217-x", "article-title": "Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy", "author": "Vezzani", "doi-asserted-by": "crossref", "first-page": "459", "journal-title": "Nat. Rev. Neurol.", "key": "ref_3", "volume": "15", "year": "2019" }, { "DOI": "10.1016/j.scib.2025.02.036", "article-title": "Nanoengineered, ultrasmall and catalytic potassium calcium hexacyanoferrate for neuroprotection and temporal lobe epilepsy treatment", "author": "Feng", "doi-asserted-by": "crossref", "first-page": "1627", "journal-title": "Sci. Bull.", "key": "ref_4", "volume": "70", "year": "2025" }, { "DOI": "10.1002/ana.23567", "article-title": "Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage", "author": "Librizzi", "doi-asserted-by": "crossref", "first-page": "82", "journal-title": "Ann. Neurol.", "key": "ref_5", "volume": "72", "year": "2012" }, { "DOI": "10.1016/j.neuron.2024.03.017", "article-title": "Microglial P2Y(6) calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis", "author": "Umpierre", "doi-asserted-by": "crossref", "first-page": "1959", "journal-title": "Neuron", "key": "ref_6", "volume": "112", "year": "2024" }, { "DOI": "10.1016/j.redox.2024.103168", "doi-asserted-by": "crossref", "key": "ref_7", "unstructured": "Liang, L.P., Sri Hari, A., Day, B.J., and Patel, M. (2024). Pharmacological elevation of glutathione inhibits status epilepticus-induced neuroinflammation and oxidative injury. Redox Biol., 73." }, { "DOI": "10.1016/j.nbd.2023.106027", "doi-asserted-by": "crossref", "key": "ref_8", "unstructured": "Villasana-Salazar, B., and Vezzani, A. (2023). Neuroinflammation microenvironment sharpens seizure circuit. Neurobiol. Dis., 178." }, { "DOI": "10.1016/j.msard.2020.102535", "article-title": "How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms", "author": "Nikbakht", "doi-asserted-by": "crossref", "first-page": "102535", "journal-title": "Mult. Scler. Relat. Disord.", "key": "ref_9", "volume": "46", "year": "2020" }, { "DOI": "10.1111/epi.16524", "article-title": "New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study", "author": "Lu", "doi-asserted-by": "crossref", "first-page": "e49", "journal-title": "Epilepsia", "key": "ref_10", "volume": "61", "year": "2020" }, { "DOI": "10.1016/j.bbi.2020.06.008", "article-title": "A brewing storm: The neuropsychological sequelae of hyperinflammation due to COVID-19", "author": "Cothran", "doi-asserted-by": "crossref", "first-page": "957", "journal-title": "Brain Behav. Immun.", "key": "ref_11", "volume": "88", "year": "2020" }, { "DOI": "10.1186/s40035-024-00458-1", "article-title": "SARS-CoV-2 membrane protein induces neurodegeneration via affecting Golgi-mitochondria interaction", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "68", "journal-title": "Transl. Neurodegener.", "key": "ref_12", "volume": "13", "year": "2024" }, { "DOI": "10.1136/jnnp-2020-324337", "article-title": "Epileptiform activity and seizures in patients with COVID-19", "author": "Issa", "doi-asserted-by": "crossref", "first-page": "565", "journal-title": "J. Neurol. Neurosurg. Psychiatry", "key": "ref_13", "volume": "92", "year": "2021" }, { "DOI": "10.1212/WNL.0000000000201651", "article-title": "The Significance of the Increased Incidence of New Onset Seizures and Epilepsy After a COVID-19 Infection", "author": "Bensken", "doi-asserted-by": "crossref", "first-page": "359", "journal-title": "Neurology", "key": "ref_14", "volume": "100", "year": "2023" }, { "DOI": "10.1212/WNL.0000000000200195", "article-title": "Risk of COVID-19 Infection and of Severe Complications Among People With Epilepsy: A Nationwide Cohort Study", "author": "Yoo", "doi-asserted-by": "crossref", "first-page": "e1886", "journal-title": "Neurology", "key": "ref_15", "volume": "98", "year": "2022" }, { "DOI": "10.3390/ijms25073819", "doi-asserted-by": "crossref", "key": "ref_16", "unstructured": "Chagas, L.D.S., and Serfaty, C.A. (2024). The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond. Int. J. Mol. Sci., 25." }, { "DOI": "10.1186/1756-6606-5-18", "article-title": "Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats", "author": "Yang", "doi-asserted-by": "crossref", "first-page": "18", "journal-title": "Mol. Brain", "key": "ref_17", "volume": "5", "year": "2012" }, { "DOI": "10.1016/j.lfs.2023.121562", "article-title": "Hepatoprotective potential of gabapentin in cecal ligation and puncture-induced sepsis; targeting oxidative stress, apoptosis, and NF-kB/MAPK signaling pathways", "author": "Abdelnaser", "doi-asserted-by": "crossref", "first-page": "121562", "journal-title": "Life Sci.", "key": "ref_18", "volume": "320", "year": "2023" }, { "DOI": "10.3390/ph10040093", "doi-asserted-by": "crossref", "key": "ref_19", "unstructured": "Rossi, A., Murta, V., Auzmendi, J., and Ramos, A.J. (2017). Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy. Pharm., 10." }, { "DOI": "10.3389/fphar.2025.1500475", "doi-asserted-by": "crossref", "key": "ref_20", "unstructured": "Deng, N.J., Li, X.Y., Zhang, Z.X., Xian-Yu, C.Y., Tao, Y.T., Ma, Y.T., Li, H.J., Gao, T.Y., Liu, X., and Luo, J. (2025). Effectiveness and safety of single anti-seizure medication as adjunctive therapy for drug-resistant focal epilepsy based on network meta-analysis. Front. Pharmacol., 16." }, { "DOI": "10.3346/jkms.2013.28.2.308", "article-title": "Intrathecal gabapentin increases interleukin-10 expression and inhibits pro-inflammatory cytokine in a rat model of neuropathic pain", "author": "Lee", "doi-asserted-by": "crossref", "first-page": "308", "journal-title": "J. Korean Med. Sci.", "key": "ref_21", "volume": "28", "year": "2013" }, { "DOI": "10.1136/bcr-2021-243459", "article-title": "Neuropathic pain post-COVID-19: A case report", "author": "McWilliam", "doi-asserted-by": "crossref", "first-page": "e243459", "journal-title": "BMJ Case Rep.", "key": "ref_22", "volume": "14", "year": "2021" }, { "DOI": "10.1111/crj.13529", "article-title": "The effectiveness of gabapentin and gabapentin/montelukast combination compared with dextromethorphan in the improvement of COVID-19- related cough: A randomized, controlled clinical trial", "author": "Soltani", "doi-asserted-by": "crossref", "first-page": "604", "journal-title": "Clin. Respir. J.", "key": "ref_23", "volume": "16", "year": "2022" }, { "DOI": "10.1002/wjo2.176", "article-title": "Clinical studies in COVID-related olfactory disorders: Review of an institutional experience", "author": "Tharakan", "doi-asserted-by": "crossref", "first-page": "129", "journal-title": "World J. Otorhinolaryngol. Head. Neck Surg.", "key": "ref_24", "volume": "10", "year": "2024" }, { "DOI": "10.1002/alr.23117", "article-title": "Gabapentin improves parosmia after COVID-19 infection", "author": "Garcia", "doi-asserted-by": "crossref", "first-page": "1034", "journal-title": "Int. Forum Allergy Rhinol.", "key": "ref_25", "volume": "13", "year": "2023" }, { "article-title": "[Vertical transmission of SARS-CoV-2. Impact on the nervous system]", "first-page": "S215", "journal-title": "Rev. Med. Inst. Mex. Seguro Soc.", "key": "ref_26", "volume": "58", "year": "2020" }, { "DOI": "10.1016/S0140-6736(21)00095-7", "article-title": "Neuropathology associated with SARS-CoV-2 infection", "author": "Egervari", "doi-asserted-by": "crossref", "first-page": "276", "journal-title": "Lancet", "key": "ref_27", "volume": "397", "year": "2021" }, { "article-title": "High rate of epilepsy in young individuals who died with COVID-19", "author": "Lempriere", "first-page": "65", "journal-title": "Nat. Rev. Neurol.", "key": "ref_28", "volume": "18", "year": "2022" }, { "DOI": "10.1212/WNL.0000000000200367", "article-title": "Epilepsy and COVID-19’s Double-Edged Sword: More Severe Disease and Delayed Epilepsy Care", "author": "Berg", "doi-asserted-by": "crossref", "first-page": "779", "journal-title": "Neurology", "key": "ref_29", "volume": "98", "year": "2022" }, { "DOI": "10.3390/antiox12051020", "doi-asserted-by": "crossref", "key": "ref_30", "unstructured": "Kim, J.E., Lee, D.S., Kim, T.H., Park, H., and Kang, T.C. (2023). Distinct Roles of CK2- and AKT-Mediated NF-kappaB Phosphorylations in Clasmatodendrosis (Autophagic Astroglial Death) within the Hippocampus of Chronic Epilepsy Rats. Antioxidants, 12." }, { "DOI": "10.1016/j.phrs.2021.105877", "article-title": "TLR4 and AT1R mediate blood-brain barrier disruption, neuroinflammation, and autonomic dysfunction in spontaneously hypertensive rats", "author": "Mowry", "doi-asserted-by": "crossref", "first-page": "105877", "journal-title": "Pharmacol. Res.", "key": "ref_31", "volume": "174", "year": "2021" }, { "DOI": "10.1161/CIRCULATIONAHA.108.814582", "article-title": "Myeloid-related protein-8/14 is critical for the biological response to vascular injury", "author": "Croce", "doi-asserted-by": "crossref", "first-page": "427", "journal-title": "Circulation", "key": "ref_32", "volume": "120", "year": "2009" }, { "DOI": "10.1016/j.bbi.2019.08.195", "article-title": "TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex", "author": "Larsen", "doi-asserted-by": "crossref", "first-page": "279", "journal-title": "Brain Behav. Immun.", "key": "ref_33", "volume": "82", "year": "2019" }, { "DOI": "10.1016/j.bbi.2024.05.023", "article-title": "Opposing effects of the purinergic P2X7 receptor on seizures in neurons and microglia in male mice", "author": "Alves", "doi-asserted-by": "crossref", "first-page": "121", "journal-title": "Brain Behav. Immun.", "key": "ref_34", "volume": "120", "year": "2024" }, { "DOI": "10.3389/fimmu.2019.00121", "doi-asserted-by": "crossref", "key": "ref_35", "unstructured": "Owens, G.C., Garcia, A.J., Mochizuki, A.Y., Chang, J.W., Reyes, S.D., Salamon, N., Prins, R.M., Mathern, G.W., and Fallah, A. (2019). Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients. Front. Immunol., 10." }, { "DOI": "10.1161/ATVBAHA.122.318721", "article-title": "Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19", "author": "Goonewardena", "doi-asserted-by": "crossref", "first-page": "1124", "journal-title": "Arterioscler. Thromb. Vasc. Biol.", "key": "ref_36", "volume": "44", "year": "2024" }, { "DOI": "10.1016/j.bbi.2020.12.026", "article-title": "Platelet endothelial cell adhesion molecule-1 is a gatekeeper of neutrophil transendothelial migration in ischemic stroke", "author": "Winneberger", "doi-asserted-by": "crossref", "first-page": "277", "journal-title": "Brain Behav. Immun.", "key": "ref_37", "volume": "93", "year": "2021" }, { "DOI": "10.1038/s41590-020-00828-7", "article-title": "Proinflammatory IgG Fc structures in patients with severe COVID-19", "author": "Chakraborty", "doi-asserted-by": "crossref", "first-page": "67", "journal-title": "Nat. Immunol.", "key": "ref_38", "volume": "22", "year": "2021" }, { "DOI": "10.1016/j.nbd.2014.11.009", "article-title": "Role of fractalkine-CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain", "author": "Ali", "doi-asserted-by": "crossref", "first-page": "194", "journal-title": "Neurobiol. Dis.", "key": "ref_39", "volume": "74", "year": "2015" }, { "DOI": "10.1016/j.jneuroim.2011.03.005", "article-title": "The roles of fractalkine/CX3CR1 system in neuronal death following pilocarpine-induced status epilepticus", "author": "Yeo", "doi-asserted-by": "crossref", "first-page": "93", "journal-title": "J. Neuroimmunol.", "key": "ref_40", "volume": "234", "year": "2011" }, { "DOI": "10.1111/imcb.12464", "article-title": "Monocytes and macrophages in severe COVID-19—Friend, foe or both?", "author": "Dress", "doi-asserted-by": "crossref", "first-page": "561", "journal-title": "Immunol. Cell Biol.", "key": "ref_41", "volume": "99", "year": "2021" }, { "DOI": "10.2147/DDDT.S314076", "article-title": "Baicalin Rescues Cognitive Dysfunction, Mitigates Neurodegeneration, and Exerts Anti-Epileptic Effects Through Activating TLR4/MYD88/Caspase-3 Pathway in Rats", "author": "Yang", "doi-asserted-by": "crossref", "first-page": "3163", "journal-title": "Drug Des. Devel Ther.", "key": "ref_42", "volume": "15", "year": "2021" }, { "DOI": "10.1186/s13578-020-00387-2", "doi-asserted-by": "crossref", "key": "ref_43", "unstructured": "Liu, L., Xu, Y., Dai, H., Tan, S., Mao, X., and Chen, Z. (2020). Dynorphin activation of kappa opioid receptor promotes microglial polarization toward M2 phenotype via TLR4/NF-kappaB pathway. Cell Biosci., 10." }, { "DOI": "10.1080/14728222.2021.1918103", "article-title": "TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2", "author": "Kaushik", "doi-asserted-by": "crossref", "first-page": "491", "journal-title": "Expert. Opin. Ther. Targets", "key": "ref_44", "volume": "25", "year": "2021" }, { "DOI": "10.20944/preprints202309.2036.v2", "doi-asserted-by": "crossref", "key": "ref_45", "unstructured": "Kyriatzis, G., Bernard, A., Bole, A., Khrestchatisky, M., and Ferhat, L. (2024). In the Rat Hippocampus, Pilocarpine-Induced Status Epilepticus Is Associated with Reactive Glia and Concomitant Increased Expression of CD31, PDGFRbeta, and Collagen IV in Endothelial Cells and Pericytes of the Blood-Brain Barrier. Int. J. Mol. Sci., 25." }, { "DOI": "10.1016/j.ajt.2023.12.005", "article-title": "Natural killer cell functional genetics and donor-specific antibody-triggered microvascular inflammation", "author": "Diebold", "doi-asserted-by": "crossref", "first-page": "743", "journal-title": "Am. J. Transplant.", "key": "ref_46", "volume": "24", "year": "2024" }, { "DOI": "10.1002/eji.201646837", "article-title": "CD69: From activation marker to metabolic gatekeeper", "author": "Cibrian", "doi-asserted-by": "crossref", "first-page": "946", "journal-title": "Eur. J. Immunol.", "key": "ref_47", "volume": "47", "year": "2017" }, { "DOI": "10.1016/j.brainres.2015.07.034", "article-title": "Epigenetics and therapeutic targets mediating neuroprotection", "author": "Qureshi", "doi-asserted-by": "crossref", "first-page": "265", "journal-title": "Brain Res.", "key": "ref_48", "volume": "1628", "year": "2015" }, { "DOI": "10.1016/j.jhep.2015.08.033", "article-title": "NF-kappaB/RelA and Nrf2 cooperate to maintain hepatocyte integrity and to prevent development of hepatocellular adenoma", "author": "Kohler", "doi-asserted-by": "crossref", "first-page": "94", "journal-title": "J. Hepatol.", "key": "ref_49", "volume": "64", "year": "2016" }, { "DOI": "10.1007/s11481-023-10091-w", "article-title": "beta-Sitosterol Alleviates Neuropathic Pain by Affect Microglia Polarization through Inhibiting TLR4/NF-kappaB Signaling Pathway", "author": "Zheng", "doi-asserted-by": "crossref", "first-page": "690", "journal-title": "J. Neuroimmune Pharmacol.", "key": "ref_50", "volume": "18", "year": "2023" }, { "DOI": "10.1016/j.bbi.2021.04.007", "article-title": "Microglial IL-10 and beta-endorphin expression mediates gabapentinoids antineuropathic pain", "author": "Ahmad", "doi-asserted-by": "crossref", "first-page": "344", "journal-title": "Brain Behav. Immun.", "key": "ref_51", "volume": "95", "year": "2021" }, { "DOI": "10.1016/j.pharmthera.2021.107989", "article-title": "CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases", "author": "Subbarayan", "doi-asserted-by": "crossref", "first-page": "107989", "journal-title": "Pharmacol. Ther.", "key": "ref_52", "volume": "231", "year": "2022" }, { "DOI": "10.1001/jama.2022.13659", "article-title": "Growing Role of Gabapentin in Opioid-Related Overdoses Highlights Misuse Potential and Off-label Prescribing Practices", "author": "Kuehn", "doi-asserted-by": "crossref", "first-page": "1283", "journal-title": "JAMA", "key": "ref_53", "volume": "328", "year": "2022" }, { "DOI": "10.3390/medicines10090052", "doi-asserted-by": "crossref", "key": "ref_54", "unstructured": "Rissardo, J.P., Medeiros Araujo de Matos, U., and Fornari Caprara, A.L. (2023). Gabapentin-Associated Movement Disorders: A Literature Review. Medicines, 10." }, { "DOI": "10.5146/tjpath.2025.14236", "doi-asserted-by": "crossref", "key": "ref_55", "unstructured": "El-Kattan, M.A., Saeed, E., Khattab, M.A., Maksoud, F., Eldein, M.E., Abdel-Roaf, N.E., Awad, W., and Elshatory, A. (2025). Gabapentin-Induced Sub-Chronic Neurotoxicity in Rats and the Protective Role of Alpha-Tocopherol. Turk. Patoloji Derg., Online ahead of print." } ], "reference-count": 55, "references-count": 55, "relation": {}, "resource": { "primary": { "URL": "https://www.mdpi.com/2227-9059/13/9/2133" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "CX3CR1–TLR4 Axis as a Shared Neuroimmune Target in COVID-19 and Epilepsy: Integrative Transcriptomics and Gabapentin Repositioning", "type": "journal-article", "volume": "13" }