{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:32:20Z","timestamp":1787585540777,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Glia-mediated inflammation contributes to a wide range of central nervous system (CNS) disorders, including epilepsy. Pregabalin (PGB) and cannabidiol (CBD) are CNS-acting drugs prescribed for various neuropsychiatric conditions, especially seizures. This study investigated the effects of PGB and CBD on glial properties in an astrocyte\u2013microglia co-culture model of inflammation. Methods: Physiological (M5, containing 5\u201310% microglia) and pathological inflammatory astrocyte\u2013microglia co-cultures (M30, containing 30\u201340% microglia) were collected from the postnatal brain hemispheres of Wistar rats (P0-P2) according to an established protocol and treated with different concentrations of PGB (3, 10, 30 and 60 \u00b5g\/mL) for 24 h or CBD (50, 500 and 1000 ng\/mL) for 1 h or 24 h. Metabolic activity was assessed by the MTT assay. Microglial phenotypes and astroglial connexin (Cx)43 expression were detected by immunocytochemistry. Results: In M5 co-cultures, short-term incubation (1 h) with high concentrations (1000 ng\/mL) of CBD significantly reduced glial viability (p &lt; 0.05), while no significant changes were observed in M30 co-cultures. After 24 h of incubation, M5 cultures exhibited a significant increase in metabolic activity at 50 ng\/mL (p &lt; 0.0001) and 500 ng\/mL (p &lt; 0.05), and a reduction at 1000 ng\/mL (p &lt; 0.05), suggesting impaired viability at high concentrations under physiological conditions. The distribution of microglial phenotypes in physiological M5 co-cultures incubated with CBD remained unchanged. In M30 co-cultures, CBD incubation for 1 and 24 h significantly reduced microglial activation and promoted a shift from reactive, phagocytic to homeostatic, ramified microglial phenotype (p &lt; 0.05, p &lt; 0.01, p &lt; 0.0001). In contrast, PGB did not affect glial cell viability, microglial phenotypes or Cx43 expression in physiological and inflammatory co-cultures, indicating that the mechanisms of action of PGB probably do not include modulation of glial cells in vitro. Conclusions: The inhibition of microglial reactivity by CBD suggests potential positive effects on the neuroinflammatory component involved in the pathogenesis of CNS disorders such as epilepsy.<\/jats:p>","DOI":"10.3390\/ph19091342","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:49:34Z","timestamp":1787582974000},"page":"1342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduction of Microglial Reactivity by Cannabidiol: Preliminary Data Obtained in an Astrocyte\u2013Microglia Co-Culture Model of Inflammation"],"prefix":"10.3390","volume":"19","author":[{"given":"Laura","family":"Sch\u00f6nfelder","sequence":"first","affiliation":[{"name":"Department of Neuroanatomy and Molecular Brain Research, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoning","family":"An","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy and Molecular Brain Research, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Reusch","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M.","family":"Faustmann","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy and Molecular Brain Research, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo Jendrik","family":"Faustmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University, 40629 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-8056","authenticated-orcid":false,"given":"Fatme S.","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical Faculty, Ruhr University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev.med.051408.105018","article-title":"Diagnosis and Treatment of Neuropsychiatric Disorders","volume":"61","author":"Taber","year":"2010","journal-title":"Annu. Rev. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.clinthera.2007.01.013","article-title":"Pregabalin: A Novel Gamma-Aminobutyric Acid Analogue in the Treatment of Neuropathic Pain, Partial-Onset Seizures, and Anxiety Disorders","volume":"29","author":"Tassone","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_3","first-page":"CD007076","article-title":"Pregabalin for Acute and Chronic Pain in Adults","volume":"3","author":"Moore","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.eplepsyres.2006.09.008","article-title":"Pharmacology and Mechanism of Action of Pregabalin: The Calcium Channel Alpha2-Delta (Alpha2-Delta) Subunit as a Target for Antiepileptic Drug Discovery","volume":"73","author":"Taylor","year":"2007","journal-title":"Epilepsy Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100345","DOI":"10.1016\/j.cdc.2020.100345","article-title":"Impact of Conformational and Solubility Properties on Psycho-Activity of Cannabidiol (CBD) and Tetrahydrocannabinol (THC)","volume":"26","author":"Palheta","year":"2020","journal-title":"Chem. Data Collect."},{"key":"ref_6","first-page":"705","article-title":"Marihuana","volume":"18","author":"Adams","year":"1942","journal-title":"Bull. N. Y. Acad. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1001\/jamaneurol.2020.0073","article-title":"Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs. Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial","volume":"77","author":"Miller","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/jamaneurol.2020.4607","article-title":"Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial","volume":"78","author":"Thiele","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1714631","article-title":"Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome","volume":"378","author":"Devinsky","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/epi4.12956","article-title":"Consensus Panel Recommendations for the Optimization of EPIDIOLEX\u00ae Treatment for Seizures Associated with Lennox\u2013Gastaut Syndrome, Dravet Syndrome, and Tuberous Sclerosis Complex","volume":"9","author":"Wechsler","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41582-019-0284-z","article-title":"Cannabinoids and the Expanded Endocannabinoid System in Neurological Disorders","volume":"16","author":"Cristino","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.expneurol.2017.08.017","article-title":"Mechanisms of Action of Cannabidiol in Adoptively Transferred Experimental Autoimmune Encephalomyelitis","volume":"298","author":"Torres","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.yebeh.2017.07.014","article-title":"Anticonvulsant Effect of Cannabidiol in the Pentylenetetrazole Model: Pharmacological Mechanisms, Electroencephalographic Profile, and Brain Cytokine Levels","volume":"75","author":"Vilela","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.seizure.2012.03.001","article-title":"Cannabidiol Exerts Anti-Convulsant Effects in Animal Models of Temporal Lobe and Partial Seizures","volume":"21","author":"Jones","year":"2012","journal-title":"Seizure"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s11064-017-2287-8","article-title":"Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP)","volume":"42","author":"Klein","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1111\/epi.16973","article-title":"Antiseizure Effects of the Cannabinoids in the Amygdala-Kindling Model","volume":"62","author":"Fallah","year":"2021","journal-title":"Epilepsia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/sj.bjp.0707133","article-title":"Cannabidiol Displays Unexpectedly High Potency as an Antagonist of CB1 and CB2 Receptor Agonists in Vitro","volume":"150","author":"Thomas","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Do Val-da Silva, R.A., Peixoto-Santos, J.E., Kandratavicius, L., De Ross, J.B., Esteves, I., De Martinis, B.S., Alves, M.N.R., Scandiuzzi, R.C., Hallak, J.E.C., and Zuardi, A.W. (2017). Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00131"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s40265-019-01171-4","article-title":"Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy","volume":"79","author":"Franco","year":"2019","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.neubiorev.2020.01.014","article-title":"The Anticonvulsant Effects of Cannabidiol in Experimental Models of Epileptic Seizures: From Behavior and Mechanisms to Clinical Insights","volume":"111","author":"Leite","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neuropharm.2013.03.027","article-title":"Mechanisms of Cannabidiol Neuroprotection in Hypoxic-Ischemic Newborn Pigs: Role of 5HT(1A) and CB2 Receptors","volume":"71","author":"Pazos","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s42238-025-00274-y","article-title":"Beyond the Hype: A Comprehensive Exploration of CBD\u2019s Biological Impacts and Mechanisms of Action","volume":"7","author":"Swenson","year":"2025","journal-title":"J. Cannabis Res."},{"key":"ref_24","first-page":"33","article-title":"Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence","volume":"9","author":"Cata","year":"2015","journal-title":"Subst. Abus."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/bs.irn.2024.03.006","article-title":"Cannabidiol and Addiction","volume":"177","author":"Moreira","year":"2024","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.euroneuro.2017.08.430","article-title":"How Addictive Are Gabapentin and Pregabalin? A Systematic Review","volume":"27","author":"Bonnet","year":"2017","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1586\/14737175.2016.1171144","article-title":"Targeting Astrocytes in Bipolar Disorder","volume":"16","author":"Peng","year":"2016","journal-title":"Expert. Rev. Neurother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejphar.2013.01.072","article-title":"Importance of Glial Activation in Neuropathic Pain","volume":"716","author":"Mika","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.neubiorev.2017.09.014","article-title":"Major Depressive Disorder and Anxiety Disorders from the Glial Perspective: Etiological Mechanisms, Intervention and Monitoring","volume":"83","author":"Sild","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00406-020-01107-0","article-title":"Lateralization of Increased Density of Iba1-Immunopositive Microglial Cells in the Anterior Midcingulate Cortex of Schizophrenia and Bipolar Disorder","volume":"270","author":"Benali","year":"2020","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41583-019-0126-4","article-title":"Neuron-Glia Interactions in the Pathophysiology of Epilepsy","volume":"20","author":"Patel","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/glia.23006","article-title":"Microglia-Neuron Communication in Epilepsy","volume":"65","author":"Eyo","year":"2017","journal-title":"Glia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0165-0173(94)00015-H","article-title":"Microglia: Intrinsic Immuneffector Cell of the Brain","volume":"20","author":"Gehrmann","year":"1995","journal-title":"Brain Res. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/glia.10141","article-title":"Microglia Activation Influences Dye Coupling and Cx43 Expression of the Astrocytic Network","volume":"42","author":"Faustmann","year":"2003","journal-title":"Glia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Siracusa, R., Fusco, R., and Cuzzocrea, S. (2019). Astrocytes: Role and Functions in Brain Pathologies. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01114"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0166-2236(98)01349-6","article-title":"Tripartite Synapses: Glia, the Unacknowledged Partner","volume":"22","author":"Araque","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1523\/JNEUROSCI.11-05-01421.1991","article-title":"Gap Junctions between Cultured Astrocytes: Immunocytochemical, Molecular, and Electrophysiological Analysis","volume":"11","author":"Dermietzel","year":"1991","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0896-6273(91)90128-M","article-title":"Gap Junctions in Cultured Astrocytes: Single-Channel Currents and Characterization of Channel-Forming Protein","volume":"6","author":"Giaume","year":"1991","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrn2757","article-title":"Astroglial Networks: A Step Further in Neuroglial and Gliovascular Interactions","volume":"11","author":"Giaume","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mylvaganam, S., Ramani, M., Krawczyk, M., and Carlen, P.L. (2014). Roles of Gap Junctions, Connexins, and Pannexins in Epilepsy. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00172"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1471-4159.2009.06431.x","article-title":"Hippocampal Seizures Alter the Expression of the Pannexin and Connexin Transcriptome","volume":"112","author":"Mylvaganam","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/abbs\/gmz038","article-title":"The Role of Connexin43 in Neuropathic Pain Induced by Spinal Cord Injury","volume":"51","author":"Wang","year":"2019","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/glia.22384","article-title":"Astrocytic CX43 Hemichannels and Gap Junctions Play a Crucial Role in Development of Chronic Neuropathic Pain Following Spinal Cord Injury","volume":"60","author":"Chen","year":"2012","journal-title":"Glia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1093\/brain\/awu140","article-title":"Connexin-43 Induces Chemokine Release from Spinal Cord Astrocytes to Maintain Late-Phase Neuropathic Pain in Mice","volume":"137","author":"Chen","year":"2014","journal-title":"Brain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrneurol.2010.178","article-title":"The Role of Inflammation in Epilepsy","volume":"7","author":"Vezzani","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neuropharm.2012.04.004","article-title":"The Role of Inflammation in Epileptogenesis","volume":"69","author":"Vezzani","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/2042098611411127","article-title":"New Generation Antiepileptic Drugs: What Do They Offer in Terms of Improved Tolerability and Safety?","volume":"2","author":"French","year":"2011","journal-title":"Ther. Adv. Drug Saf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/nrn.2018.2","article-title":"Microglia in Neuropathic Pain: Cellular and Molecular Mechanisms and Therapeutic Potential","volume":"19","author":"Inoue","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1523\/JNEUROSCI.2566-20.2021","article-title":"The Modulatory Effect of Motor Cortex Astrocytes on Diabetic Neuropathic Pain","volume":"41","author":"Lu","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/nn1992","article-title":"The Neuropathic Pain Triad: Neurons, Immune Cells and Glia","volume":"10","author":"Scholz","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/j.pain.0000000000001122","article-title":"Inflammation in the Pathophysiology of Neuropathic Pain","volume":"159","author":"Sommer","year":"2018","journal-title":"Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.it.2020.07.007","article-title":"The Role of Astrocytes in CNS Inflammation","volume":"41","author":"Giovannoni","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Faustmann, T.J., Corvace, F., Faustmann, P.M., and Ismail, F.S. (2025). Influence of Antipsychotic Drugs on Microglia-Mediated Neuroinflammation in Schizophrenia: Perspectives in an Astrocyte-Microglia Co-Culture Model. Front. Psychiatry, 16.","DOI":"10.3389\/fpsyt.2025.1522128"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/epi.12473","article-title":"Glia and Epilepsy: Experimental Investigation of Antiepileptic Drugs in an Astroglia\/Microglia Co-Culture Model of Inflammation","volume":"55","author":"Dambach","year":"2014","journal-title":"Epilepsia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"174696","DOI":"10.1016\/j.ejphar.2021.174696","article-title":"Anti-Inflammatory Properties of Lacosamide in an Astrocyte-Microglia Co-Culture Model of Inflammation","volume":"915","author":"Corvace","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ismail, F.S., Corvace, F., Faustmann, P.M., and Faustmann, T.J. (2021). Pharmacological Investigations in Glia Culture Model of Inflammation. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.805755"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jnr.21639","article-title":"Implications of Antiinflammatory Properties of the Anticonvulsant Drug Levetiracetam in Astrocytes","volume":"86","author":"Haghikia","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/ijnp\/pyab080","article-title":"Effects of Lamotrigine and Topiramate on Glial Properties in an Astrocyte-Microglia Co-Culture Model of Inflammation","volume":"25","author":"Faustmann","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ismail, F.S., Faustmann, P.M., K\u00fcmmel, M.-L., F\u00f6rster, E., Faustmann, T.J., and Corvace, F. (2022). Brivaracetam Exhibits Mild Pro-Inflammatory Features in an in Vitro Astrocyte-Microglia Co-Culture Model of Inflammation. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.995861"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1007\/s00210-023-02538-x","article-title":"Tiagabine and Zonisamide Differentially Regulate the Glial Properties in an Astrocyte-Microglia Co-Culture Model of Inflammation","volume":"396","author":"Ismail","year":"2023","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Alles, S.R.A., Cain, S.M., and Snutch, T.P. (2020). Pregabalin as a Pain Therapeutic: Beyond Calcium Channels. Front. Cell Neurosci., 14.","DOI":"10.3389\/fncel.2020.00083"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/bph.16035","article-title":"Differential Regulation of Cav 3.2 and Cav 2.2 Calcium Channels by CB1 Receptors and Cannabidiol","volume":"180","author":"Harding","year":"2023","journal-title":"Br. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12640-024-00692-5","article-title":"High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System","volume":"42","author":"Romariz","year":"2024","journal-title":"Neurotox. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.envpol.2013.07.046","article-title":"Biphasic Dose Responses in Biology, Toxicology and Medicine: Accounting for Their Generalizability and Quantitative Features","volume":"182","author":"Calabrese","year":"2013","journal-title":"Environ. Pollut."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1017\/S1461145712001502","article-title":"The Anxiolytic Effect of Cannabidiol on Chronically Stressed Mice Depends on Hippocampal Neurogenesis: Involvement of the Endocannabinoid System","volume":"16","author":"Campos","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.4049\/jimmunol.1401844","article-title":"Critical Role of Mast Cells and Peroxisome Proliferator-Activated Receptor \u03b3 in the Induction of Myeloid-Derived Suppressor Cells by Marijuana Cannabidiol In Vivo","volume":"194","author":"Hegde","year":"2015","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00011.2010","article-title":"Physiology of Microglia","volume":"91","author":"Kettenmann","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/glia.23738","article-title":"Cannabidiol Prevents LPS-Induced Microglial Inflammation by Inhibiting ROS\/NF-\u03baB-Dependent Signaling and Glucose Consumption","volume":"68","author":"Michel","year":"2020","journal-title":"Glia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1074\/jbc.M109.069294","article-title":"Cannabinoids Delta(9)-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-Activated NF-kappaB and Interferon-Beta\/STAT Proinflammatory Pathways in BV-2 Microglial Cells","volume":"285","author":"Kozela","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Pes\u00e1ntez R\u00edos, G., Perucca, E., Striano, P., Caraballo, R., Pes\u00e1ntez R\u00edos, X., Pascual-Pascual, S.I., and Pes\u00e1ntez Cuesta, G. (2025). Epilepsy, Neuroinflammation and Cannabidiol What Do We Know Thus Far?. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1749260"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3346\/jkms.2011.26.3.404","article-title":"Pregabalin as a Neuroprotector after Spinal Cord Injury in Rats: Biochemical Analysis and Effect on Glial Cells","volume":"26","author":"Ha","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s00586-008-0653-6","article-title":"Pregabalin as a Neuroprotector after Spinal Cord Injury in Rats","volume":"17","author":"Ha","year":"2008","journal-title":"Eur. Spine J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.neuroscience.2016.12.037","article-title":"Pregabalin Enhances Myelin Repair and Attenuates Glial Activation in Lysolecithin-Induced Demyelination Model of Rat Optic Chiasm","volume":"344","author":"Daneshdoust","year":"2017","journal-title":"Neuroscience"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/brb3.276","article-title":"Impact of Pregabalin Treatment on Synaptic Plasticity and Glial Reactivity during the Course of Experimental Autoimmune Encephalomyelitis","volume":"4","author":"Silva","year":"2014","journal-title":"Brain Behav."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1038\/s41598-020-61006-1","article-title":"Pregabalin Inhibits in Vivo and in Vitro Cytokine Secretion and Attenuates Spleen Inflammation in Lipopolysaccharide\/Concanavalin A -Induced Murine Models of Inflammation","volume":"10","author":"Mansour","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bbi.2021.04.007","article-title":"Microglial IL-10 and \u03b2-Endorphin Expression Mediates Gabapentinoids Antineuropathic Pain","volume":"95","author":"Ahmad","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0306-4522(02)00533-X","article-title":"Involvement of Electrical Coupling in the in Vivo Ictal Epileptiform Activity Induced by 4-Aminopyridine in the Neocortex","volume":"115","author":"Szente","year":"2002","journal-title":"Neuroscience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1111\/j.0013-9580.2003.25803.x","article-title":"Involvement of Gap Junctions in the Manifestation and Control of the Duration of Seizures in Rats in Vivo","volume":"44","author":"Gajda","year":"2003","journal-title":"Epilepsia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/sj.bjp.0704776","article-title":"The Extracellular Regulated Kinases (ERK) 1\/2 Mediate Cannabinoid-Induced Inhibition of Gap Junctional Communication in Endothelial Cells","volume":"136","author":"Brandes","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/glia.20223","article-title":"Effects of Cytokines on Microglial Phenotypes and Astroglial Coupling in an Inflammatory Coculture Model","volume":"52","author":"Hinkerohe","year":"2005","journal-title":"Glia"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.brainres.2010.03.012","article-title":"Dexamethasone Prevents LPS-Induced Microglial Activation and Astroglial Impairment in an Experimental Bacterial Meningitis Co-Culture Model","volume":"1329","author":"Hinkerohe","year":"2010","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/01.ftd.0000158874.54100.1a","article-title":"Analysis of Pregabalin at Therapeutic Concentrations in Human Plasma\/Serum by Reversed-Phase HPLC","volume":"27","author":"Berry","year":"2005","journal-title":"Ther. Drug Monit."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.eplepsyres.2005.11.001","article-title":"Activity Profile of Pregabalin in Rodent Models of Epilepsy and Ataxia","volume":"68","author":"Vartanian","year":"2006","journal-title":"Epilepsy Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1213\/ANE.0b013e31825d2ad1","article-title":"The Immunomodulatory Effect of Pregabalin on Spleen Cells in Neuropathic Mice","volume":"115","author":"Jang","year":"2012","journal-title":"Anesth. Analg."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Silva, G.D., Del Guerra, F.B., de Oliveira Lelis, M., and Pinto, L.F. (2020). Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.531939"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.yebeh.2019.03.042","article-title":"Higher Cannabidiol Plasma Levels Are Associated with Better Seizure Response Following Treatment with a Pharmaceutical Grade Cannabidiol","volume":"95","author":"Szaflarski","year":"2019","journal-title":"Epilepsy Behav."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:58:10Z","timestamp":1787583490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/9\/1342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":86,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ph19091342"],"URL":"https:\/\/doi.org\/10.3390\/ph19091342","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}