{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:41:28Z","timestamp":1788500488712,"version":"build-2803163510"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS110648 NS120916"],"award-info":[{"award-number":["NS110648 NS120916"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Glial scars have been observed following stab lesions in the spinal cord and brain but not observed and characterized in chemoconvulsant-induced epilepsy models. Epilepsy is a disorder characterized by spontaneous recurrent seizures and can be modeled in rodents. Diisopropylfluorophosphate (DFP) exposure, like other real-world organophosphate nerve agents (OPNAs) used in chemical warfare scenarios, can lead to the development of <jats:italic>status epilepticus<\/jats:italic> (SE). We have previously demonstrated that DFP-induced SE promotes epileptogenesis which is characterized by the development of spontaneous recurrent seizures (SRS), gliosis, and neurodegeneration. In this study, we report classical glial scars developed in the piriform cortex, but not in the hippocampus, by 8\u00a0days post-exposure. We challenged both male and female rats with 4\u20135\u00a0mg\/kg DFP (s.c.) followed immediately by 2\u00a0mg\/kg atropine sulfate (i.m.) and 25\u00a0mg\/kg pralidoxime (i.m.) and one hour later by midazolam (i.m). Glial scars were present in the piriform cortex\/amygdala region in 73% of the DFP treated animals. No scars were found in controls. Scars were characterized by a massive clustering of reactive microglia surrounded by hypertrophic reactive astrocytes. The core of the scars was filled with a significant increase of IBA1 and CD68 positive cells and a significant reduction in NeuN positive cells compared to the periphery of the scars. There was a significantly higher density of reactive GFAP, complement 3 (C3), and inducible nitric oxide synthase (iNOS) positive cells at the periphery of the scar compared to similar areas in controls. We found a significant increase in chondroitin sulfate proteoglycans (CS-56) in the periphery of the scars compared to a similar region in control brains. However, there was no change in TGF-\u03b21 or TGF-\u03b22 positive cells in or around the scars in DFP-exposed animals compared to controls. In contrast to stab-induced scars, we did not find fibroblasts (Thy1.1) in the scar core or periphery. There were sex differences with respect to the density of iNOS, CD68, NeuN, GFAP, C3 and CS-56 positive cells. This is the first report of cortical glial scars in rodents with systemic chemoconvulsant-induced SE. Further investigation could help to elucidate the mechanisms of scar development and mitigation strategies.<\/jats:p>","DOI":"10.3389\/fcell.2022.867949","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T06:32:52Z","timestamp":1647412372000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of Cortical Glial Scars in the Diisopropylfluorophosphate (DFP) Rat Model of Epilepsy"],"prefix":"10.3389","volume":"10","author":[{"given":"Meghan","family":"Gage","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Gard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thimmasettappa","family":"Thippeswamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial Interactions at the Blood-Brain Barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/NATURE17623","article-title":"Astrocyte Scar Formation Aids central Nervous System Axon Regeneration","volume":"532","author":"Anderson","year":"2016","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/NYAS.13028","article-title":"Long-term Neuropathological and Behavioral Impairments after Exposure to Nerve Agents","volume":"1374","author":"Aroniadou-Anderjaska","year":"2016","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.neuro.2009.06.011","article-title":"Primary Brain Targets of Nerve Agents: The Role of the Amygdala in Comparison to the hippocampus","volume":"30","author":"Aroniadou-Anderjaska","year":"2009","journal-title":"NeuroToxicology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/642798","article-title":"Chondroitin Sulfate Proteoglycans: Structure-Function Relationship with Implication in Neural Development and Brain Disorders","volume":"2014","author":"Avram","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1002\/ana.24147","article-title":"Losartan Prevents Acquired Epilepsy via TGF-\u03b2 Signaling Suppression","volume":"75","author":"Bar-Klein","year":"2014","journal-title":"Ann. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/J.1749-6632.2003.TB03138.X","article-title":"Activation of Complement in the Central Nervous System","volume":"992","author":"Beek","year":"2003","journal-title":"Ann. N Y Acad. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1111\/epi.12579","article-title":"Prevalence of Epilepsy-An Unknown Quantity","volume":"55","author":"Beghi","year":"2014","journal-title":"Epilepsia"},{"key":"B9","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1212\/WNL.0000000000002875","article-title":"Astrocyte Signaling and Synaptic Homeostasis","volume":"87","author":"Benarroch","year":"2016","journal-title":"Neurology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/sj.sc.3102148","article-title":"TGF-\u03b21 and TGF-\u03922 Expression after Traumatic Human Spinal Cord Injury","volume":"46","author":"Buss","year":"2007","journal-title":"Spinal Cord"},{"key":"B11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/J.EXPNEUROL.2005.01.004","article-title":"Growth-associated Gene Expression after Stroke: Evidence for a Growth-Promoting Region in Peri-Infarct Cortex","volume":"193","author":"Carmichael","year":"2005","journal-title":"Exp. Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nrn3484","article-title":"Emerging Roles of Astrocytes in Neural Circuit Development","volume":"14","author":"Clarke","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1369\/0022155412464638","article-title":"An Introduction to Proteoglycans and Their Localization","volume":"60","author":"Couchman","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/J.EXPNEUROL.2013.12.024","article-title":"Functional Regeneration beyond the Glial Scar","volume":"253","author":"Cregg","year":"2014","journal-title":"Exp. Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jneumeth.2008.04.019","article-title":"The Pilocarpine Model of Temporal Lobe Epilepsy","volume":"172","author":"Curia","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncel.2014.00362","article-title":"The Impact of Microglial Activation on Blood-Brain Barrier in Brain Diseases","volume":"8","author":"da Fonseca","year":"2014","journal-title":"Front. Cel. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"5810","DOI":"10.1523\/JNEUROSCI.19-14-05810.1999","article-title":"Robust Regeneration of Adult Sensory Axons in Degenerating White Matter of the Adult Rat Spinal Cord","volume":"19","author":"Davies","year":"1999","journal-title":"J. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3146230","DOI":"10.1038\/125230a0","article-title":"Degeneration and Regeneration of the Nervous System","volume":"125","author":"Db","year":"1930","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/J.BRAINRES.2004.12.016","article-title":"Expression of Neurocan after Transient Middle Cerebral Artery Occlusion in Adult Rat Brain","volume":"1037","author":"Deguchi","year":"2005","journal-title":"Brain Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.2337\/DIABETES.54.8.2305","article-title":"Expression of CD68 and Macrophage Chemoattractant Protein-1 Genes in Human Adipose and Muscle Tissues","volume":"54","author":"Di Gregorio","year":"2005","journal-title":"Diabetes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"8219","DOI":"10.3390\/IJMS13078219","article-title":"The Neuroprotective Functions of Transforming Growth Factor Beta Proteins","volume":"13","author":"Dobolyi","year":"2012","journal-title":"Ijms"},{"key":"B22","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1007\/S12264-011-1530-6","article-title":"Nitric Oxide in Neurodegeneration: Potential Benefits of Non-steroidal Anti-inflammatories","volume":"27","author":"Doherty","year":"2011","journal-title":"Neurosci. Bull."},{"key":"B23","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41583-021-00525-w","article-title":"Emerging Roles for CNS Fibroblasts in Health, Injury and Disease","volume":"2323","author":"Dorrier","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"13360","DOI":"10.1073\/PNAS.1510176112\/-\/DCSUPPLEMENTAL","article-title":"Transcriptome Analyses Reveal Molecular Mechanisms Underlying Functional Recovery after Spinal Cord Injury","volume":"112","author":"Duan","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/0306-4522(91)90269-T","article-title":"Glial Changes Following an Excitotoxic Lesion in the CNS-II. Astrocytes","volume":"45","author":"Dusart","year":"1991","journal-title":"Neuroscience"},{"key":"B26","doi-asserted-by":"publisher","first-page":"12","DOI":"10.4103\/0972-2327.128644","article-title":"Approaches to Refractory Epilepsy","volume":"17","author":"Engel","year":"2014","journal-title":"Ann. Indian Acad. Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/978-3-319-57193-5_12","article-title":"Neurodegeneration and Pathology in Epilepsy: Clinical and Basic Perspectives","volume":"15","author":"Farrell","year":"2017","journal-title":"Adv. Neurobiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/S0361-9230(99)00072-6","article-title":"The Glial Scar and central Nervous System Repair","volume":"49","author":"Fawcett","year":"1999","journal-title":"Brain Res. Bull."},{"key":"B29","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/j.0013-9580.2005.66104.x","article-title":"Epileptic Seizures and Epilepsy: Definitions Proposed by the International League against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)","volume":"46","author":"Fisher","year":"2005","journal-title":"Epilepsia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/0167-5699(91)90009-I","article-title":"The Role of Complement in Inflammation and Phagocytosis","volume":"12","author":"Frank","year":"1991","journal-title":"Immunol. Today"},{"key":"B31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1528-1167.2007.00992.x","article-title":"Refractory Epilepsy: Clinical Overview","volume":"48","author":"French","year":"2007","journal-title":"Epilepsia"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e45294","DOI":"10.15252\/EMBR.201745294","article-title":"Cross\u2010talk between Monocyte Invasion and Astrocyte Proliferation Regulates Scarring in Brain Injury","volume":"19","author":"Frik","year":"2018","journal-title":"EMBO Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/nyas.14315","article-title":"Sex as a Biological Variable in the Rat Model of Diisopropylfluorophosphate\u2010induced Long\u2010term Neurotoxicity","volume":"1479","author":"Gage","year":"2020","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3389\/FNCEL.2021.772868","article-title":"Differential Impact of Severity and Duration of Status Epilepticus, Medical Countermeasures, and a Disease-Modifier, Saracatinib, on Brain Regions in the Rat Diisopropylfluorophosphate Model","volume":"15","author":"Gage","year":"","journal-title":"Front. Cel. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3390\/ANTIOX11010061","article-title":"Saracatinib, a Src Tyrosine Kinase Inhibitor, as a Disease Modifier in the Rat DFP Model: Sex Differences, Neurobehavior, Gliosis, Neurodegeneration, and Nitro-Oxidative Stress","volume":"11","author":"Gage","year":"","journal-title":"Antioxidants"},{"key":"B36","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.expneurol.2014.10.017","article-title":"The Role of the Nitric Oxide Pathway in Brain Injury and its Treatment - from Bench to Bedside","volume":"263","author":"Garry","year":"2015","journal-title":"Exp. Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"104431","DOI":"10.1016\/j.nbd.2019.03.019","article-title":"Persistent Behavior Deficits, Neuroinflammation, and Oxidative Stress in a Rat Model of Acute Organophosphate Intoxication","volume":"133","author":"Guignet","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/S40478-019-0735-1\/FIGURES\/7","article-title":"Complement 3+-astrocytes Are Highly Abundant in Prion Diseases, but Their Abolishment Led to an Accelerated Disease Course and Early Dysregulation of Microglia","volume":"7","author":"Hartmann","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.3390\/CELLS10061382","article-title":"TGF-\u03b2\/Smad Signalling in Neurogenesis: Implications for Neuropsychiatric Diseases","volume":"10","author":"Hiew","year":"2021","journal-title":"Cells"},{"key":"B40","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1212\/01.wnl.0000252807.38124.a3","article-title":"How Common Are the \u201cCommon\u201d Neurologic Disorders?","volume":"68","author":"Hirtz","year":"2007","journal-title":"Neurology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/FNCEL.2020.00208\/BIBTEX","article-title":"Role of Chondroitin Sulfation Following Spinal Cord Injury","volume":"14","author":"Hussein","year":"2020","journal-title":"Front. Cel. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/J.MATBIO.2015.02.003","article-title":"Proteoglycan Form and Function: A Comprehensive Nomenclature of Proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1016\/J.NEURO.2012.10.005","article-title":"Chemical Toxins that Cause Seizures","volume":"33","author":"Jett","year":"2012","journal-title":"NeuroToxicology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1093\/ABBS\/GMX124","article-title":"The Role of TGF-\u03b2 Superfamily Signaling in Neurological Disorders","volume":"50","author":"Kashima","year":"2018","journal-title":"Acta Biochim. Biophys. Sinica"},{"key":"B45","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/S00441-012-1336-5","article-title":"Role of the Lesion Scar in the Response to Damage and Repair of the central Nervous System","volume":"349","author":"Kawano","year":"2012","journal-title":"Cell Tissue Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1006\/MCNE.2002.1121","article-title":"Expression of TGF\u03b22 but Not TGF\u03b21 Correlates with the Deposition of Scar Tissue in the Lesioned Spinal Cord","volume":"20","author":"Lagord","year":"2002","journal-title":"Mol. Cell Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.nurt.2010.08.002","article-title":"Astrocytes and Epilepsy","volume":"7","author":"Lanerolle","year":"2010","journal-title":"Neurotherapeutics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"112","DOI":"10.4103\/2152-7806.83732","article-title":"Spinal Cord Injury: From Inflammation to Glial Scar","volume":"2","author":"Leal-Filho","year":"2011","journal-title":"Surg. Neurol. Int."},{"key":"B49","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3727\/096368916X693824","article-title":"The Regulatory Effects of Transforming Growth Factor-\u03b2 on Nerve Regeneration","volume":"26","author":"Li","year":"2017","journal-title":"Cel Transpl."},{"key":"B50","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-06505-6","article-title":"Modulation of Proteoglycan Receptor PTP\u03c3 Enhances MMP-2 Activity to Promote Recovery from Multiple Sclerosis","volume":"9","author":"Luo","year":"2018","journal-title":"Nat. Commun."},{"key":"B52","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S0149-7634(96)00050-4","article-title":"Neuropharmacological Mechanisms of Nerve Agent-Induced Seizure and Neuropathology 1 1The Animals Used in Studies Performed in, or Sponsored by, This Institute Were Handled in Accordance with the Principles Stated in the Guide for the Care and Use of Laboratory Animals, Proposed by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council, DHHA, National Institute of Health Publication #85-23, 1985, and the Animal Welfare Act of 1966, as Amended. The Opinions, or Assertions Contained Herein Are the Private Views of the Authors, and Are Not to Be Construed as Reflecting the Views of the Department of the Army or the Department of Defense","volume":"21","author":"McDonough","year":"1997","journal-title":"Neurosci. Biobehavioral Rev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"10778","DOI":"10.1523\/JNEUROSCI.19-24-10778.1999","article-title":"The Chondroitin Sulfate Proteoglycans Neurocan and Phosphacan Are Expressed by Reactive Astrocytes in the Chronic CNS Glial Scar","volume":"19","author":"McKeon","year":"1999","journal-title":"J. Neurosci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"7032","DOI":"10.1021\/bi982678l","article-title":"Crystal Structures of Aged Phosphonylated Acetylcholinesterase: Nerve Agent Reaction Products at the Atomic Level,","volume":"38","author":"Millard","year":"1999","journal-title":"Biochemistry"},{"key":"B55","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1539\/joh.47.299","article-title":"Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack","volume":"47","author":"Miyaki","year":"2005","journal-title":"Jrnl Occup. Health"},{"key":"B56","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/s0140-6736(95)92170-2","article-title":"Sarin Poisoning in Matsumoto, Japan","volume":"346","author":"Morita","year":"1995","journal-title":"Lancet"},{"key":"B57","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s0196-0644(96)70052-5","article-title":"Report on 640 Victims of the Tokyo Subway Sarin Attack","volume":"28","author":"Okumura","year":"1996","journal-title":"Ann. Emerg. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/J.BBADIS.2015.11.014","article-title":"Reactive Gliosis in the Pathogenesis of CNS Diseases","volume":"1862","author":"Pekny","year":"2016","journal-title":"Biochim. Biophys. Acta (Bba) - Mol. Basis Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-11410-x","article-title":"Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss","volume":"7","author":"Peterson","year":"2017","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1165\/AJRCMB\/1.1.65","article-title":"Characterization of Two Major Populations of Lung Fibroblasts: Distinguishing Morphology and Discordant Display of Thy 1 and Class II MHC","volume":"1","author":"Phipps","year":"1989","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/S13311-014-0257-2","article-title":"Past and Present Definitions of Epileptogenesis and its Biomarkers","volume":"11","author":"Pitk\u00e4nen","year":"2014","journal-title":"Neurotherapeutics"},{"key":"B62","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1111\/J.1460-9568.2005.03876.X","article-title":"Chondroitin 6-sulphate Synthesis Is Up-Regulated in Injured CNS, Induced by Injury-Related Cytokines and Enhanced in Axon-Growth Inhibitory Glia","volume":"21","author":"Properzi","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/nyas.14314","article-title":"Diapocynin, an NADPH Oxidase Inhibitor, Counteracts Diisopropylfluorophosphate\u2010induced Long\u2010term Neurotoxicity in the Rat Model","volume":"1479","author":"Putra","year":"","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"104443","DOI":"10.1016\/j.nbd.2019.03.031","article-title":"Inducible Nitric Oxide Synthase Inhibitor, 1400W, Mitigates DFP-Induced Long-Term Neurotoxicity in the Rat Model","volume":"133","author":"Putra","year":"","journal-title":"Neurobiol. Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.nbd.2016.05.013","article-title":"1400W, a Highly Selective Inducible Nitric Oxide Synthase Inhibitor Is a Potential Disease Modifier in the Rat Kainate Model of Temporal Lobe Epilepsy","volume":"93","author":"Puttachary","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of Seizure Activity by Electrical Stimulation: II. Motor Seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalography Clin. Neurophysiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"14833","DOI":"10.1073\/PNAS.93.25.14833","article-title":"Cell Surface Expression of Mouse Macrosialin and Human CD68 and Their Role as Macrophage Receptors for Oxidized Low Density Lipoprotein","volume":"93","author":"Ramprasad","year":"1996","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-018-1192-7","article-title":"The Role of Inflammation in the Development of Epilepsy","volume":"15","author":"Rana","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"B69","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1177\/1073858416645498","article-title":"Astroglial Scarring and Seizures","volume":"23","author":"Robel","year":"2017","journal-title":"Neuroscientist"},{"key":"B70","doi-asserted-by":"publisher","first-page":"3330","DOI":"10.1523\/JNEUROSCI.1574-14.2015","article-title":"Reactive Astrogliosis Causes the Development of Spontaneous Seizures","volume":"35","author":"Robel","year":"2015","journal-title":"J. Neurosci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nrn2591","article-title":"The Bright Side of the Glial Scar in CNS Repair","volume":"10","author":"Rolls","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-21662-x","article-title":"Drebrin Controls Scar Formation and Astrocyte Reactivity upon Traumatic Brain Injury by Regulating Membrane Trafficking","volume":"12","author":"Schiweck","year":"2021","journal-title":"Nat. Commun."},{"key":"B73","doi-asserted-by":"publisher","first-page":"a022830","DOI":"10.1101\/cshperspect.a022830","article-title":"Status Epilepticus","volume":"6","author":"Seinfeld","year":"2016","journal-title":"Cold Spring Harb Perspect. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"105410","DOI":"10.1016\/j.nbd.2021.105410","article-title":"Mechanisms of Disease-Modifying Effect of Saracatinib (AZD0530), a Src\/Fyn Tyrosine Kinase Inhibitor, in the Rat Kainate Model of Temporal Lobe Epilepsy","volume":"156","author":"Sharma","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/845323","article-title":"Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair","volume":"2014","author":"Siebert","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B76","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/nrn1326","article-title":"Regeneration beyond the Glial Scar","volume":"5","author":"Silver","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/NRN3898","article-title":"Astrocyte Barriers to Neurotoxic Inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1177\/1073858405278321","article-title":"Reactive Astrocytes in Neural Repair and protection","volume":"11","author":"Sofroniew","year":"2005","journal-title":"Neuroscientist"},{"key":"B79","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1007\/S12031-019-01361-5","article-title":"TGF-\u03b2 Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro","volume":"69","author":"Song","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"a022426","DOI":"10.1101\/CSHPERSPECT.A022426","article-title":"Seizures and Epilepsy: An Overview for Neuroscientists","volume":"5","author":"Stafstrom","year":"2015","journal-title":"Cold Spring Harbor Perspect. Med."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/JN.1940.3.1.1","article-title":"SPINAL CORD REGENERATION IN THE RAT","volume":"3","author":"Sugar","year":"1940","journal-title":"J. Neurophysiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/s0140-6736(95)90726-2","article-title":"Sarin Poisoning in Tokyo Subway","volume":"345","author":"Suzuki","year":"1995","journal-title":"The Lancet"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1172\/JCI27341","article-title":"Deficiency in Neuronal TGF-\u03b2 Signaling Promotes Neurodegeneration and Alzheimer's Pathology","volume":"116","author":"Tesseur","year":"2006","journal-title":"J. Clin. Invest."},{"key":"B84","doi-asserted-by":"publisher","first-page":"445","DOI":"10.14670\/HH-21.445","article-title":"Nitric Oxide, a Biological Double-Faced Janus-Iis This Good or Bad?","volume":"21","author":"Thippeswamy","year":"2006","journal-title":"Histol. Histopathol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.eplepsyres.2012.04.014","article-title":"Characterization of Status Epilepticus Induced by Two Organophosphates in Rats","volume":"101","author":"Todorovic","year":"2012","journal-title":"Epilepsy Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"625017","DOI":"10.3389\/FNEUR.2021.625017","article-title":"The Impacts of Surgery and Intracerebral Electrodes in C57BL\/6J Mouse Kainate Model of Epileptogenesis: Seizure Threshold, Proteomics, and Cytokine Profiles","volume":"12","author":"Tse","year":"2021","journal-title":"Front. Neurol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.3389\/FNEUR.2020.591690\/BIBTEX","article-title":"Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis","volume":"11","author":"Verhoog","year":"2020","journal-title":"Front. Neurol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1586\/14737175.2015.1079130","article-title":"Immunity and Inflammation in Status Epilepticus and its Sequelae: Possibilities for Therapeutic Application","volume":"15","author":"Vezzani","year":"2015","journal-title":"Expert Rev. Neurotherapeutics"},{"key":"B89","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/J.CYTOGFR.2005.09.011","article-title":"Transforming Growth Factor-\u03b2 Signalling in Brain Disorders","volume":"17","author":"Vivien","year":"2006","journal-title":"Cytokine Growth Factor. Rev."},{"key":"B90","doi-asserted-by":"publisher","first-page":"11511","DOI":"10.1523\/JNEUROSCI.1514-09.2009","article-title":"Reactive Astrocytes Form Scar-like Perivascular Barriers to Leukocytes during Adaptive Immune Inflammation of the CNS","volume":"29","author":"Voskuhl","year":"2009","journal-title":"J. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nrd3011","article-title":"Therapeutic Potential of Complement Modulation","volume":"9","author":"Wagner","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"B92","doi-asserted-by":"publisher","first-page":"205873841880140","DOI":"10.1177\/2058738418801406","article-title":"Portrait of Glial Scar in Neurological Diseases","volume":"31","author":"Wang","year":"2018","journal-title":"Int. J. Immunopathol Pharmacol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"12870","DOI":"10.1523\/JNEUROSCI.2121-13.2013","article-title":"Glial Scar Borders Are Formed by Newly Proliferated, Elongated Astrocytes that Interact to Corral Inflammatory and Fibrotic Cells via STAT3-dependent Mechanisms after Spinal Cord Injury","volume":"33","author":"Wanner","year":"2013","journal-title":"J. Neurosci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1161\/STROKEAHA.120.033431","article-title":"Central Nervous System Fibroblast-like Cells in Stroke and Other Neurological Disorders","volume":"52","author":"Xu","year":"2021","journal-title":"Stroke"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3389\/FNEUR.2019.01149\/BIBTEX","article-title":"Role of Astrocytes in Post-traumatic Epilepsy","volume":"10","author":"Xu","year":"2019","journal-title":"Front. Neurol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jns.2006.06.007","article-title":"Sarin Experiences in Japan: Acute Toxicity and Long-Term Effects","volume":"249","author":"Yanagisawa","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"B97","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/FNCEL.2020.00078\/BIBTEX","article-title":"Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury","volume":"14","author":"Yang","year":"2020","journal-title":"Front. Cel. Neurosci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/J.AJPATH.2016.11.010","article-title":"Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes\/Macrophages after Spinal Cord Injury","volume":"187","author":"Yokota","year":"2017","journal-title":"Am. J. Pathol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/S12264-013-1358-3","article-title":"The glial scar in Spinal Cord Injury and Repair","volume":"29","author":"Yuan","year":"2013","journal-title":"Neurosci. Bull."},{"key":"B100","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/J.EXPNEUROL.2015.07.009","article-title":"Involvement of Chondroitin 6-sulfation in Temporal Lobe Epilepsy","volume":"274","author":"Yutsudo","year":"2015","journal-title":"Exp. Neurol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.867949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T06:32:57Z","timestamp":1647412377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.867949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":100,"alternative-id":["10.3389\/fcell.2022.867949"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.867949","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]},"article-number":"867949"}}