{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:29:14Z","timestamp":1762900154189},"reference-count":124,"publisher":"Aging and Disease","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging and disease"],"published-print":{"date-parts":[[2021]]},"DOI":"10.14336\/ad.2021.0129","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T17:41:37Z","timestamp":1625334097000},"page":"1056","source":"Crossref","is-referenced-by-count":7,"title":["Novel Concepts for the Role of Chloride Cotransporters in Refractory Seizures"],"prefix":"10.14336","volume":"12","author":[{"given":"Pavel A","family":"Kipnis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpa D","family":"Kadam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5462","reference":[{"key":"key-10.14336\/AD.2021.0129-1","doi-asserted-by":"crossref","unstructured":"Scharfman HE (2007). The neurobiology of epilepsy. Curr Neurol Neurosci Rep, 7:348-354.","DOI":"10.1007\/s11910-007-0053-z"},{"key":"key-10.14336\/AD.2021.0129-2","doi-asserted-by":"crossref","unstructured":"Kang SK, Kadam SD (2015). Neonatal Seizures: Impact on Neurodevelopmental Outcomes. Frontiers in Pediatrics, 3:101.","DOI":"10.3389\/fped.2015.00101"},{"key":"key-10.14336\/AD.2021.0129-3","doi-asserted-by":"crossref","unstructured":"Staley K (2015). Molecular mechanisms of epilepsy. Nat Neurosci, 18:367-372.","DOI":"10.1038\/nn.3947"},{"key":"key-10.14336\/AD.2021.0129-4","doi-asserted-by":"crossref","unstructured":"Jensen FE (2006). Pediatric epilepsy models. Epilepsy Res, 68:28-31.","DOI":"10.1016\/j.eplepsyres.2005.09.013"},{"key":"key-10.14336\/AD.2021.0129-5","doi-asserted-by":"crossref","unstructured":"Auvin S, Pineda E, Shin D, Gressens P, Mazarati A (2012). Novel Animal Models of Pediatric Epilepsy. Neurotherapeutics, 9:245-261.","DOI":"10.1007\/s13311-012-0119-8"},{"key":"key-10.14336\/AD.2021.0129-6","doi-asserted-by":"crossref","unstructured":"Pitk\u00e4nen A, Engel J (2014). Past and Present Definitions of Epileptogenesis and Its Biomarkers. Neurotherapeutics, 11:231-241.","DOI":"10.1007\/s13311-014-0257-2"},{"key":"key-10.14336\/AD.2021.0129-7","doi-asserted-by":"crossref","unstructured":"Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, et al (2016). Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study. J Pediatr, 174:98-103.e1.","DOI":"10.1016\/j.jpeds.2016.03.035"},{"key":"key-10.14336\/AD.2021.0129-8","doi-asserted-by":"crossref","unstructured":"Glass HC, Numis AL, Gano D, Bali V, Rogers EE (2018). Outcomes After Acute Symptomatic Seizures in Children Admitted to a Neonatal Neurocritical Care Service. Pediatr Neurol, 84:39-45.","DOI":"10.1016\/j.pediatrneurol.2018.03.016"},{"key":"key-10.14336\/AD.2021.0129-9","doi-asserted-by":"crossref","unstructured":"Liu S, Yu W, L\u00fc Y (2016). The causes of new-onset epilepsy and seizures in the elderly. Neuropsychiatr Dis Treat, 12:1425-1434.","DOI":"10.2147\/NDT.S107905"},{"key":"key-10.14336\/AD.2021.0129-10","doi-asserted-by":"crossref","unstructured":"Sen A, Jette N, Husain M, Sander JW (2020). Epilepsy in older people. Lancet, 395:735-748.","DOI":"10.1016\/S0140-6736(19)33064-8"},{"key":"key-10.14336\/AD.2021.0129-11","doi-asserted-by":"crossref","unstructured":"Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al (2014). ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 55:475-482.","DOI":"10.1111\/epi.12550"},{"key":"key-10.14336\/AD.2021.0129-12","doi-asserted-by":"crossref","unstructured":"L\u00f6scher W (2017). Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs. Neurochem Res, 42:1873-1888.","DOI":"10.1007\/s11064-017-2222-z"},{"key":"key-10.14336\/AD.2021.0129-13","doi-asserted-by":"crossref","unstructured":"Fritschy J-M, Panzanelli P (2014). GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. Eur J Neurosci, 39:1845-1865.","DOI":"10.1111\/ejn.12534"},{"key":"key-10.14336\/AD.2021.0129-14","doi-asserted-by":"crossref","unstructured":"Walker MC, Semyanov A (2008). Regulation of excitability by extrasynaptic GABA(A) receptors. Results Probl Cell Differ, 44:29-48.","DOI":"10.1007\/400_2007_030"},{"key":"key-10.14336\/AD.2021.0129-15","doi-asserted-by":"crossref","unstructured":"Zheleznova NN, Sedelnikova A, Weiss DS (2009). Function and modulation of \u03b4-containing GABAA receptors. Psychoneuroendocrinology, 34S1:S67-S73.","DOI":"10.1016\/j.psyneuen.2009.08.010"},{"key":"key-10.14336\/AD.2021.0129-16","doi-asserted-by":"crossref","unstructured":"Contestabile A, Magara S, Cancedda L (2017). The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome. Front Cell Neurosci. doi: .","DOI":"10.3389\/fncel.2017.00054"},{"key":"key-10.14336\/AD.2021.0129-17","doi-asserted-by":"crossref","unstructured":"Kuczewski N, Fuchs C, Ferrand N, Jovanovic JN, Gaiarsa J-L, Porcher C (2011). Mechanism of GABAB receptor-induced BDNF secretion and promotion of GABAA receptor membrane expression. J Neurochem, 118:533-545.","DOI":"10.1111\/j.1471-4159.2011.07192.x"},{"key":"key-10.14336\/AD.2021.0129-18","doi-asserted-by":"crossref","unstructured":"Rost BR, Nicholson P, Ahnert-Hilger G, Rummel A, Rosenmund C, Breustedt J, et al (2011). Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion. J Cell Sci, 124:3066-3073.","DOI":"10.1242\/jcs.074963"},{"key":"key-10.14336\/AD.2021.0129-19","doi-asserted-by":"crossref","unstructured":"Banerjee PN, Filippi D, Hauser WA (2009). The descriptive epidemiology of epilepsy-a review. Epilepsy Res, 85:31-45.","DOI":"10.1016\/j.eplepsyres.2009.03.003"},{"key":"key-10.14336\/AD.2021.0129-20","unstructured":"Volpe JJ (1981). Neurology of the newborn. Major Probl Clin Pediatr, 22:1-648."},{"key":"key-10.14336\/AD.2021.0129-21","doi-asserted-by":"crossref","unstructured":"French Jacqueline A (2007). Refractory Epilepsy: Clinical Overview. Epilepsia, 48:3-7.","DOI":"10.1111\/j.1528-1167.2007.00992.x"},{"key":"key-10.14336\/AD.2021.0129-22","doi-asserted-by":"crossref","unstructured":"Kempermann G (2015). Adult Neurogenesis: An Evolutionary Perspective. Cold Spring Harb Perspect Biol, 8:a018986.","DOI":"10.1101\/cshperspect.a018986"},{"key":"key-10.14336\/AD.2021.0129-23","doi-asserted-by":"crossref","unstructured":"Cuzon VC, Yeh PW, Cheng Q, Yeh HH (2006). Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence. Cereb Cortex, 16:1377-1388.","DOI":"10.1093\/cercor\/bhj084"},{"key":"key-10.14336\/AD.2021.0129-24","doi-asserted-by":"crossref","unstructured":"Cancedda L (2007). Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo. J Neurosci, 27:5224-5235.","DOI":"10.1523\/JNEUROSCI.5169-06.2007"},{"key":"key-10.14336\/AD.2021.0129-25","doi-asserted-by":"crossref","unstructured":"Dieni CV, Chancey JH, Overstreet-Wadiche LS (2012). Dynamic functions of GABA signaling during granule cell maturation. Front Neural Circuits, 6:113.","DOI":"10.3389\/fncir.2012.00113"},{"key":"key-10.14336\/AD.2021.0129-26","doi-asserted-by":"crossref","unstructured":"Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997). Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci, 17:3727-3738.","DOI":"10.1523\/JNEUROSCI.17-10-03727.1997"},{"key":"key-10.14336\/AD.2021.0129-27","doi-asserted-by":"crossref","unstructured":"Huttenlocher PR, de Courten C, Garey LJ, Van der Loos H (1982). Synaptogenesis in human visual cortex--evidence for synapse elimination during normal development. Neurosci Lett, 33:247-252.","DOI":"10.1016\/0304-3940(82)90379-2"},{"key":"key-10.14336\/AD.2021.0129-28","doi-asserted-by":"crossref","unstructured":"Sanchez RM, Jensen FE (2001). Maturational aspects of epilepsy mechanisms and consequences for the immature brain. Epilepsia, 42:577-585.","DOI":"10.1046\/j.1528-1157.2001.12000.x"},{"key":"key-10.14336\/AD.2021.0129-29","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez Fern\u00e1ndez I, Loddenkemper T (2014). Subunit Composition of Neurotransmitter Receptors in the Immature and in the Epileptic Brain. Biomed Res Int. doi: .","DOI":"10.1155\/2014\/301950"},{"key":"key-10.14336\/AD.2021.0129-30","doi-asserted-by":"crossref","unstructured":"Diering GH, Huganir RL (2018). The AMPA Receptor Code of Synaptic Plasticity. Neuron, 100:314-329.","DOI":"10.1016\/j.neuron.2018.10.018"},{"key":"key-10.14336\/AD.2021.0129-31","doi-asserted-by":"crossref","unstructured":"Kumar SS, Bacci A, Kharazia V, Huguenard JR (2002). A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons. J Neurosci, 22:3005-3015.","DOI":"10.1523\/JNEUROSCI.22-08-03005.2002"},{"key":"key-10.14336\/AD.2021.0129-32","doi-asserted-by":"crossref","unstructured":"Sanchez RM, Koh S, Rio C, Wang C, Lamperti ED, Sharma D, et al (2001). Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxia-induced seizures. J Neurosci, 21:8154-8163.","DOI":"10.1523\/JNEUROSCI.21-20-08154.2001"},{"key":"key-10.14336\/AD.2021.0129-33","doi-asserted-by":"crossref","unstructured":"Klein P, Dingledine R, Aronica E, Bernard C, Bl++mcke I, Boison D, et al (2018). Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia, 59:37-66.","DOI":"10.1111\/epi.13965"},{"key":"key-10.14336\/AD.2021.0129-34","doi-asserted-by":"crossref","unstructured":"Goldberg EM, Coulter DA (2013). Mechanisms of epileptogenesis: A convergence on neural circuit dysfunction. Nature Reviews Neuroscience, 14:337-349.","DOI":"10.1038\/nrn3482"},{"key":"key-10.14336\/AD.2021.0129-35","doi-asserted-by":"crossref","unstructured":"Dingledine R, Varvel NH, Dudek FE (2014). When and How Do Seizures Kill Neurons, and Is Cell Death Relevant to Epileptogenesis? Adv Exp Med Biol, 813:109-122.","DOI":"10.1007\/978-94-017-8914-1_9"},{"key":"key-10.14336\/AD.2021.0129-36","doi-asserted-by":"crossref","unstructured":"Buckmaster PS, Dudek FE (1997). Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J Comp Neurol, 385:385-404.","DOI":"10.1002\/(SICI)1096-9861(19970901)385:3<385::AID-CNE4>3.0.CO;2-#"},{"key":"key-10.14336\/AD.2021.0129-37","doi-asserted-by":"crossref","unstructured":"Kobayashi M, Buckmaster PS (2003). Reduced Inhibition of Dentate Granule Cells in a Model of Temporal Lobe Epilepsy. J Neurosci, 23:2440-2452.","DOI":"10.1523\/JNEUROSCI.23-06-02440.2003"},{"key":"key-10.14336\/AD.2021.0129-38","doi-asserted-by":"crossref","unstructured":"Shao L-R, Dudek FE (2011). Repetitive Perforant-Path Stimulation Induces Epileptiform Bursts in Minislices of Dentate Gyrus From Rats With Kainate-Induced Epilepsy. J Neurophysiol, 105:522-527.","DOI":"10.1152\/jn.00456.2010"},{"key":"key-10.14336\/AD.2021.0129-39","doi-asserted-by":"crossref","unstructured":"Magl\u00f3czky Z, Freund TF (2005). Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci, 28:334-340.","DOI":"10.1016\/j.tins.2005.04.002"},{"key":"key-10.14336\/AD.2021.0129-40","doi-asserted-by":"crossref","unstructured":"Burman RJ, Selfe JS, Lee JH, van den Berg M, Calin A, Codadu NK, et al (2019). Excitatory GABAergic signalling is associated with benzodiazepine resistance in status epilepticus. Brain, 142:3482-3501.","DOI":"10.1093\/brain\/awz283"},{"key":"key-10.14336\/AD.2021.0129-41","doi-asserted-by":"crossref","unstructured":"Scharfman HE, Brooks-Kayal AR (2014). Is Plasticity of GABAergic Mechanisms Relavant to Epileptogenesis? Adv Exp Med Biol, 813:133-150.","DOI":"10.1007\/978-94-017-8914-1_11"},{"key":"key-10.14336\/AD.2021.0129-42","doi-asserted-by":"crossref","unstructured":"Nardou R, Ferrari DC, Ben-Ari Y (2013). Mechanisms and effects of seizures in the immature brain. Semin Fetal Neonatal Med, 18:175-184.","DOI":"10.1016\/j.siny.2013.02.003"},{"key":"key-10.14336\/AD.2021.0129-43","doi-asserted-by":"crossref","unstructured":"Hyde TM, Lipska BK, Ali T, Mathew SV, Law AJ, Metitiri OE, et al (2011). Expression of GABA Signaling Molecules KCC2, NKCC1, and GAD1 in Cortical Development and Schizophrenia. J Neurosci, 31:11088-11095.","DOI":"10.1523\/JNEUROSCI.1234-11.2011"},{"key":"key-10.14336\/AD.2021.0129-44","doi-asserted-by":"crossref","unstructured":"Kipnis PA, Sullivan BJ, Carter BM, Kadam SD (2020). TrkB agonists prevent postischemic emergence of refractory neonatal seizures in mice. JCI Insight. doi: .","DOI":"10.1172\/jci.insight.136007"},{"key":"key-10.14336\/AD.2021.0129-45","doi-asserted-by":"crossref","unstructured":"Sullivan BJ, Kipnis PA, Carter BM, Kadam SD (2020). Targeting ischemia-induced KCC2 hypofunction rescues refractory neonatal seizures and mitigates epileptogenesis in a mouse model. bioRxiv, 2020.09.15.298596.","DOI":"10.1101\/2020.09.15.298596"},{"key":"key-10.14336\/AD.2021.0129-46","doi-asserted-by":"crossref","unstructured":"Cutler CP, Cramb G (2002). Two isoforms of the Na+\/K+\/2Cl- cotransporter are expressed in the European eel (Anguilla anguilla). Biochim Biophys Acta, 1566:92-103.","DOI":"10.1016\/S0005-2736(02)00596-5"},{"key":"key-10.14336\/AD.2021.0129-47","doi-asserted-by":"crossref","unstructured":"Begum G, Yuan H, Kahle KT, Li L, Wang S, Shi Y, et al (2015). Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery After Stroke. Stroke, 46:1956-1965.","DOI":"10.1161\/STROKEAHA.115.008939"},{"key":"key-10.14336\/AD.2021.0129-48","doi-asserted-by":"crossref","unstructured":"Kahle KT, Schmouth JF, Lavastre V, Latremoliere A, Zhang J, Andrews N, et al (2016). Inhibition of the kinase WNK1\/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. SciSignal, 9:ra32-ra32.","DOI":"10.1126\/scisignal.aad0163"},{"key":"key-10.14336\/AD.2021.0129-49","doi-asserted-by":"crossref","unstructured":"Kharod SC, Kang SK, Kadam SD (2019). Off-label use of bumetanide for brain disorders: An overview. Front Neurosci. doi: .","DOI":"10.3389\/fnins.2019.00310"},{"key":"key-10.14336\/AD.2021.0129-50","doi-asserted-by":"crossref","unstructured":"Flagella M, Clarke LL, Miller ML, Erway LC, Giannella RA, Andringa A, et al (1999). Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J Biol Chem, 274:26946-26955.","DOI":"10.1074\/jbc.274.38.26946"},{"key":"key-10.14336\/AD.2021.0129-51","doi-asserted-by":"crossref","unstructured":"St\u00f6dberg T, Magnusson M, Lesko N, Wredenberg A, Martin Munoz D, Stranneheim H, et al (2020). SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia. Neurol Genet, 6:e478.","DOI":"10.1212\/NXG.0000000000000478"},{"key":"key-10.14336\/AD.2021.0129-52","doi-asserted-by":"crossref","unstructured":"Sedmak G, Jovanov-Milo\u0161evi\u0107 N, Puskarjov M, Ulamec M, Kru\u0161lin B, Kaila K, et al (2016). Developmental Expression Patterns of KCC2 and Functionally Associated Molecules in the Human Brain. Cereb Cortex, 26:4574-4589.","DOI":"10.1093\/cercor\/bhv218"},{"key":"key-10.14336\/AD.2021.0129-53","doi-asserted-by":"crossref","unstructured":"Kaila K, Price TJ, Payne JA, Puskarjov M, Voipio J (2014). Cation-chloride cotransporters in neuronal development, plasticity and disease. Nat Rev Neurosci, 15:637-654.","DOI":"10.1038\/nrn3819"},{"key":"key-10.14336\/AD.2021.0129-54","doi-asserted-by":"crossref","unstructured":"Markkanen M, Karhunen T, Llano O, Ludwig A, Rivera C, Uvarov P, et al (2014). Distribution of neuronal KCC2a and KCC2b isoforms in mouse CNS. J Comp Neurol, 522:1897-1914.","DOI":"10.1002\/cne.23510"},{"key":"key-10.14336\/AD.2021.0129-55","doi-asserted-by":"crossref","unstructured":"Dubois CJ, Cardoit L, Schwarz V, Markkanen M, Airaksinen MS, Uvarov P, et al (2018). Role of the K+-Cl- Cotransporter KCC2a Isoform in Mammalian Respiration at Birth. eNeuro. doi: .","DOI":"10.1523\/ENEURO.0264-18.2018"},{"key":"key-10.14336\/AD.2021.0129-56","doi-asserted-by":"crossref","unstructured":"Kahle KT, Deeb TZ, Puskarjov M, Silayeva L, Liang B, Kaila K, et al (2013). Modulation of neuronal activity by phosphorylation of the K-Cl cotransporter KCC2. Trends Neurosci, 36:726-737.","DOI":"10.1016\/j.tins.2013.08.006"},{"key":"key-10.14336\/AD.2021.0129-57","doi-asserted-by":"crossref","unstructured":"Lee HHC, Walker JA, Williams JR, Goodier RJ, Payne JA, Moss SJ (2007). Direct Protein Kinase C-dependent Phosphorylation Regulates the Cell Surface Stability and Activity of the Potassium Chloride Cotransporter KCC2. J Biol Chem, 282:29777-29784.","DOI":"10.1074\/jbc.M705053200"},{"key":"key-10.14336\/AD.2021.0129-58","doi-asserted-by":"crossref","unstructured":"Lee HHC, Deeb TZ, Walker JA, Davies PA, Moss SJ (2011). NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents. Nature Neuroscience, 14:736-743.","DOI":"10.1038\/nn.2806"},{"key":"key-10.14336\/AD.2021.0129-59","doi-asserted-by":"crossref","unstructured":"de Los Heros P, Alessi DR, Gourlay R, Campbell DG, Deak M, Macartney TJ, et al (2014). The WNK-regulated SPAK\/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J, 458:559-573.","DOI":"10.1042\/BJ20131478"},{"key":"key-10.14336\/AD.2021.0129-60","doi-asserted-by":"crossref","unstructured":"Moore YE, Deeb TZ, Chadchankar H, Brandon NJ, Moss SJ (2018). Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures. PNAS, 115:10166-10171.","DOI":"10.1073\/pnas.1810134115"},{"key":"key-10.14336\/AD.2021.0129-61","doi-asserted-by":"crossref","unstructured":"Hubner CA, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch TJ (2001). Disruption of KCC2 Reveals an Essential Role of K-Cl Cotransport Already in Early Synaptic Inhibition. Neuron, 30:515-524.","DOI":"10.1016\/S0896-6273(01)00297-5"},{"key":"key-10.14336\/AD.2021.0129-62","doi-asserted-by":"crossref","unstructured":"Li H, Khirug S, Cai C, Ludwig A, Blaesse P, Kolikova J, et al (2007). KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron, 56:1019-1033.","DOI":"10.1016\/j.neuron.2007.10.039"},{"key":"key-10.14336\/AD.2021.0129-63","doi-asserted-by":"crossref","unstructured":"Ben-Ari Y (2017). NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders. Trends in Neurosciences, 40:536-554.","DOI":"10.1016\/j.tins.2017.07.001"},{"key":"key-10.14336\/AD.2021.0129-64","doi-asserted-by":"crossref","unstructured":"Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011). Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci, 14:285-293.","DOI":"10.1038\/nn.2741"},{"key":"key-10.14336\/AD.2021.0129-65","doi-asserted-by":"crossref","unstructured":"Wong M, Guo D (2013). Dendritic spine pathology in epilepsy: Cause or consequence? Neuroscience, 251:141-150.","DOI":"10.1016\/j.neuroscience.2012.03.048"},{"key":"key-10.14336\/AD.2021.0129-66","doi-asserted-by":"crossref","unstructured":"Kharod SC, Carter BM, Kadam SD (2018). Pharmaco-resistant Neonatal Seizures: Critical Mechanistic Insights from a Chemoconvulsant Model. Dev Neurobiol, 78:1117-1130.","DOI":"10.1002\/dneu.22634"},{"key":"key-10.14336\/AD.2021.0129-67","doi-asserted-by":"crossref","unstructured":"Aguado F (2003). BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+\/Cl- co-transporter KCC2. Development, 130:1267-1280.","DOI":"10.1242\/dev.00351"},{"key":"key-10.14336\/AD.2021.0129-68","unstructured":"Kang S, Kadam S (2014). Pre-Clinical Models of Acquired Neonatal Seizures: Differential Effects of Injury on Function of Chloride Co-Transporters. Austin J Cerebrovasc Dis Stroke 1:."},{"key":"key-10.14336\/AD.2021.0129-69","doi-asserted-by":"crossref","unstructured":"Carter BM, Sullivan BJ, Landers JR, Kadam SD (2018). Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal seizures by ANA12. Scientific Reports, 8:11987.","DOI":"10.1038\/s41598-018-30486-7"},{"key":"key-10.14336\/AD.2021.0129-70","doi-asserted-by":"crossref","unstructured":"Huberfeld G (2007). Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J Neurosci, 27:9866-9873.","DOI":"10.1523\/JNEUROSCI.2761-07.2007"},{"key":"key-10.14336\/AD.2021.0129-71","doi-asserted-by":"crossref","unstructured":"Gharaylou Z, Oghabian MA, Azizi Z, Hadjighassem M (2019). Brain microstructural abnormalities correlate with KCC2 downregulation in refractory epilepsy. Neuroreport, 30:409-414.","DOI":"10.1097\/WNR.0000000000001216"},{"key":"key-10.14336\/AD.2021.0129-72","doi-asserted-by":"crossref","unstructured":"Hadjikhani N, Asberg Johnels J, Lassalle A, Zurcher NR, Hippolyte L, Gillberg C, et al (2018). Bumetanide for autism: more eye contact, less amygdala activation. Scientific Reports, 8:3602.","DOI":"10.1038\/s41598-018-21958-x"},{"key":"key-10.14336\/AD.2021.0129-73","doi-asserted-by":"crossref","unstructured":"Greenfield LJ (2013). Molecular Mechanisms of Antiseizure Drug Activity at GABAA Receptors. Seizure, 22:589-600.","DOI":"10.1016\/j.seizure.2013.04.015"},{"key":"key-10.14336\/AD.2021.0129-74","doi-asserted-by":"crossref","unstructured":"Boylan GB, Pressler RM (2013). Neonatal seizures: the journey so far. SeminFetal Neonatal Med, 18:173-174.","DOI":"10.1016\/j.siny.2013.05.011"},{"key":"key-10.14336\/AD.2021.0129-75","doi-asserted-by":"crossref","unstructured":"Sullivan BJ, Kadam SD (2020). The involvement of neuronal chloride transporter deficiencies in epilepsy. In: Tang X, editor. Neuronal Chloride Transporters in Health and Disease. Academic Press, 329-366.","DOI":"10.1016\/B978-0-12-815318-5.00014-5"},{"key":"key-10.14336\/AD.2021.0129-76","doi-asserted-by":"crossref","unstructured":"Romermann K, Fedrowitz M, Hampel P, Kaczmarek E, Tollner K, ETraynelis SF, et al (2017). Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain. Neuropharmacology, 117:182-194.","DOI":"10.1016\/j.neuropharm.2017.02.006"},{"key":"key-10.14336\/AD.2021.0129-77","doi-asserted-by":"crossref","unstructured":"Kang SK, Markowitz GJ, Kim ST, Johnston MV, Kadam SD (2015). Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters. Frontiers in Cellular Neuroscience, 9:173.","DOI":"10.3389\/fncel.2015.00173"},{"key":"key-10.14336\/AD.2021.0129-78","doi-asserted-by":"crossref","unstructured":"Johne M, R\u00f6mermann K, Hampel P, Gailus B, Theilmann W, Ala-Kurikka T, et al (2020). Phenobarbital and midazolam suppress neonatal seizures in a noninvasive rat model of birth asphyxia, whereas bumetanide is ineffective. Epilepsia. doi: .","DOI":"10.1111\/epi.16778"},{"key":"key-10.14336\/AD.2021.0129-79","doi-asserted-by":"crossref","unstructured":"Mazarati A, Shin D, Sankar R (2009). Bumetanide inhibits rapid kindling in neonatal rats. Epilepsia, 50:2117-2122.","DOI":"10.1111\/j.1528-1167.2009.02048.x"},{"key":"key-10.14336\/AD.2021.0129-80","unstructured":"NCT01434225 (2015). NEMO1:NEonatal Seizure Using Medication Off-patent(NEMO1). 2015."},{"key":"key-10.14336\/AD.2021.0129-81","doi-asserted-by":"crossref","unstructured":"Soul JS, Bergin AM, Stopp C, Hayes B, Singh A, Fortuno CR, et al (2020). A pilot randomized, controlled, double-blind trial of bumetanide to treat neonatal seizures Controlled bumetanide trial for neonatal seizures. Ann Neurol. doi: .","DOI":"10.1002\/ana.25959"},{"key":"key-10.14336\/AD.2021.0129-82","doi-asserted-by":"crossref","unstructured":"Lemonnier E, Degrez C, Phelep M, Tyzio R, Josse F, Grandgeorge M, et al (2012). A randomised controlled trial of bumetanide in the treatment of autism in children. Translational Psychiatry, 2:e202.","DOI":"10.1038\/tp.2012.124"},{"key":"key-10.14336\/AD.2021.0129-83","doi-asserted-by":"crossref","unstructured":"Lemonnier E, Villeneuve N, Sonie S, Serret S, Rosier A, Roue M, et al (2017). Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders. Translational Psychiatry, 7:e1056.","DOI":"10.1038\/tp.2017.10"},{"key":"key-10.14336\/AD.2021.0129-84","doi-asserted-by":"crossref","unstructured":"Du L, Shan L, Wang B, Li H, Xu Z, Staal WG, et al (2015). A Pilot Study on the Combination of Applied Behavior Analysis and Bumetanide Treatment for Children with Autism. Journal of Child and Adolescent Psychopharmacology, 25:585-588.","DOI":"10.1089\/cap.2015.0045"},{"key":"key-10.14336\/AD.2021.0129-85","unstructured":"Hajri M, Ben Amor A, Abbes Z, Dhouib S, Ouanes S, Mrabet A, et al (2019). Bumetanide in the management of autism. Tunisian experience in Razi Hospital. Tunis Med, 97:971-977."},{"key":"key-10.14336\/AD.2021.0129-86","doi-asserted-by":"crossref","unstructured":"van Andel DM, Sprengers JJ, Oranje B, Scheepers FE, Jansen FE, Bruining H (2020). Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study. Molecular Autism, 11:30.","DOI":"10.1186\/s13229-020-00335-4"},{"key":"key-10.14336\/AD.2021.0129-87","doi-asserted-by":"crossref","unstructured":"Zhang L, Huang CC, Dai Y, Luo Q, Ji Y, Wang K, et al (2020). Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA\/glutamate ratios. Translational Psychiatry, 10:1-12.","DOI":"10.1038\/s41398-020-0747-4"},{"key":"key-10.14336\/AD.2021.0129-88","doi-asserted-by":"crossref","unstructured":"Vlaskamp C, Poil SS, Jansen F, Linkenkaer-Hansen K, Durston S, Oranje B, et al (2017). Bumetanide As a Candidate Treatment for Behavioral Problems in Tuberous Sclerosis Complex. Frontiers in Neurology, 8:469.","DOI":"10.3389\/fneur.2017.00469"},{"key":"key-10.14336\/AD.2021.0129-89","doi-asserted-by":"crossref","unstructured":"Tollner K, Brandt C, Topfer M, Brunhofer G, Erker T, Gabriel M, et al (2014). A novel prodrug-based strategy to increase effects of bumetanide in epilepsy. Ann Neurol, 75:550-562.","DOI":"10.1002\/ana.24124"},{"key":"key-10.14336\/AD.2021.0129-90","doi-asserted-by":"crossref","unstructured":"Lykke K, Tollner K, Feit PW, Erker T, MacAulay N, Loscher W (2016). The search for NKCC1-selective drugs for the treatment of epilepsy: Structure-function relationship of bumetanide and various bumetanide derivatives in inhibiting the human cation-chloride cotransporter NKCC1A. Epilepsy & Behavior, 59:42-49.","DOI":"10.1016\/j.yebeh.2016.03.021"},{"key":"key-10.14336\/AD.2021.0129-91","doi-asserted-by":"crossref","unstructured":"Romijn HJ, Hofman MA, Gramsbergen A (1991). At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby? Early Hum Dev, 26:61-67.","DOI":"10.1016\/0378-3782(91)90044-4"},{"key":"key-10.14336\/AD.2021.0129-92","doi-asserted-by":"crossref","unstructured":"Auvin S, Charriaut-Marlangue C (2017). Role of seizure in neonatal stroke. Oncotarget, 8:48531-48532.","DOI":"10.18632\/oncotarget.18212"},{"key":"key-10.14336\/AD.2021.0129-93","doi-asserted-by":"crossref","unstructured":"Bejot Y, Prigent-Tessier A, Cachia C, Giroud M, Mossiat C, Bertrand N, et al (2011). Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats. Neurochemistry International, 58:102-111.","DOI":"10.1016\/j.neuint.2010.10.019"},{"key":"key-10.14336\/AD.2021.0129-94","doi-asserted-by":"crossref","unstructured":"Medina I, Friedel P, Rivera C, Kahle KT, Kourdougli N, Uvarov P, et al (2014). Current view on the functional regulation of the neuronal K+-Cl- cotransporter KCC2. Front Cell Neurosci. doi: .","DOI":"10.3389\/fncel.2014.00027"},{"key":"key-10.14336\/AD.2021.0129-95","doi-asserted-by":"crossref","unstructured":"Lai MC, Yang SN (2011). Perinatal Hypoxic-Ischemic Encephalopathy. J Biomed Biotechnol. 2011: 609813","DOI":"10.1155\/2011\/609813"},{"key":"key-10.14336\/AD.2021.0129-96","doi-asserted-by":"crossref","unstructured":"Kokaia Z, Andsberg G, Yan Q, Lindvall O (1998). Rapid Alterations of BDNF Protein Levels in the Rat Brain after Focal Ischemia: Evidence for Increased Synthesis and Anterograde Axonal Transport. Experimental Neurology, 154:289-301.","DOI":"10.1006\/exnr.1998.6888"},{"key":"key-10.14336\/AD.2021.0129-97","doi-asserted-by":"crossref","unstructured":"Rivera C, Li H, Thomas-Crusells J, Lahtinen H, Viitanen T, Nanobashvili A, et al (2002). BDNF-induced TrkB activation down-regulates the K+-Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion. J Cell Biol, 159:747-752.","DOI":"10.1083\/jcb.200209011"},{"key":"key-10.14336\/AD.2021.0129-98","doi-asserted-by":"crossref","unstructured":"Cazorla M, Pr\u00e9mont J, Mann A, Girard N, Kellendonk C, Rognan D (2011). Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice. J Clin Invest, 121:1846-1857.","DOI":"10.1172\/JCI43992"},{"key":"key-10.14336\/AD.2021.0129-99","doi-asserted-by":"crossref","unstructured":"Feng Y, Yang H, Yue Y, Tian F (2020). MicroRNAs and target genes in epileptogenesis. Epilepsia, 61:2086-2096.","DOI":"10.1111\/epi.16687"},{"key":"key-10.14336\/AD.2021.0129-100","doi-asserted-by":"crossref","unstructured":"Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009). miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta, 1792:497-505.","DOI":"10.1016\/j.bbadis.2009.02.013"},{"key":"key-10.14336\/AD.2021.0129-101","doi-asserted-by":"crossref","unstructured":"Varendi K, Kumar A, H\u00e4rma M-A, Andressoo J-O (2014). miR-1, miR-10b, miR-155, and miR-191 are novel regulators of BDNF. Cell Mol Life Sci, 71:4443-4456.","DOI":"10.1007\/s00018-014-1628-x"},{"key":"key-10.14336\/AD.2021.0129-102","doi-asserted-by":"crossref","unstructured":"Holmes GL, Gairsa J-L, Chevassus-Au-Louis N, Ben-Ari Y (1998). Consequences of neonatal seizures in the rat: Morphological and behavioral effects. Annals of Neurology, 44:845-857.","DOI":"10.1002\/ana.410440602"},{"key":"key-10.14336\/AD.2021.0129-103","doi-asserted-by":"crossref","unstructured":"Diaz-Arrastia R, Agostini MA, Frol AB, Mickey B, Fleckenstein J, Bigio E, et al (2000). Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults. Arch Neurol, 57:1611-1616.","DOI":"10.1001\/archneur.57.11.1611"},{"key":"key-10.14336\/AD.2021.0129-104","doi-asserted-by":"crossref","unstructured":"Swartz BE, Houser CR, Tomiyasu U, Walsh GO, DeSalles A, Rich JR, et al (2006). Hippocampal cell loss in posttraumatic human epilepsy. Epilepsia, 47:1373-1382.","DOI":"10.1111\/j.1528-1167.2006.00602.x"},{"key":"key-10.14336\/AD.2021.0129-105","doi-asserted-by":"crossref","unstructured":"Pitk\u00e4nen A, Immonen R (2014). Epilepsy Related to Traumatic Brain Injury. Neurotherapeutics, 11:286-296.","DOI":"10.1007\/s13311-014-0260-7"},{"key":"key-10.14336\/AD.2021.0129-106","doi-asserted-by":"crossref","unstructured":"L\u00f6scher W, Hirsch LJ, Schmidt D (2015). The enigma of the latent period in the development of symptomatic acquired epilepsy - Traditional view versus new concepts. Epilepsy Behav, 52:78-92.","DOI":"10.1016\/j.yebeh.2015.08.037"},{"key":"key-10.14336\/AD.2021.0129-107","doi-asserted-by":"crossref","unstructured":"Chang EF, Englot DJ, Vadera S (2015). Minimally invasive surgical approaches for temporal lobe epilepsy. Epilepsy Behav, 47:24-33.","DOI":"10.1016\/j.yebeh.2015.04.033"},{"key":"key-10.14336\/AD.2021.0129-108","doi-asserted-by":"crossref","unstructured":"Helmstaedter C, Kurthen M, Lux S, Reuber M, Elger CE (2003). Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol, 54:425-432.","DOI":"10.1002\/ana.10692"},{"key":"key-10.14336\/AD.2021.0129-109","doi-asserted-by":"crossref","unstructured":"Palma E, Amici M, Sobrero F, Spinelli G, Di Angelantonio S, Ragozzino D, et al (2006). Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory. Proc Natl Acad Sci USA, 103:8465-8468.","DOI":"10.1073\/pnas.0602979103"},{"key":"key-10.14336\/AD.2021.0129-110","doi-asserted-by":"crossref","unstructured":"Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R (2002). On the Origin of Interictal Activity in Human Temporal Lobe Epilepsy in Vitro. Science, 298:1418.","DOI":"10.1126\/science.1076510"},{"key":"key-10.14336\/AD.2021.0129-111","doi-asserted-by":"crossref","unstructured":"Liu G, Gu B, He X-P, Joshi RB, Wackerle HD, Rodriguiz RM, et al (2013). Transient Inhibition of TrkB Kinase Following Status Epilepticus Prevents Development of Temporal Lobe Epilepsy. Neuron, 79:31-38.","DOI":"10.1016\/j.neuron.2013.04.027"},{"key":"key-10.14336\/AD.2021.0129-112","doi-asserted-by":"crossref","unstructured":"Huang YZ, He X-P, Krishnamurthy K, McNamara JO (2019). TrkB-Shc Signaling Protects against Hippocampal Injury Following Status Epilepticus. J Neurosci, 39:4624-4630.","DOI":"10.1523\/JNEUROSCI.2939-18.2019"},{"key":"key-10.14336\/AD.2021.0129-113","doi-asserted-by":"crossref","unstructured":"Patterson KP, Baram TZ, Shinnar S (2014). Origins of Temporal Lobe Epilepsy: Febrile Seizures and Febrile Status Epilepticus. Neurotherapeutics, 11:242-250.","DOI":"10.1007\/s13311-014-0263-4"},{"key":"key-10.14336\/AD.2021.0129-114","doi-asserted-by":"crossref","unstructured":"Shinnar R, Shinnar S, Hesdorffer DC, O\u2019Hara K, Conklin T, Cornett K, et al (2017). Parental Stress, Pediatric Quality of Life and Behavior at Baseline and One Year Follow-up: Results from the FEBSTAT Study. Epilepsy Behav, 69:95-99.","DOI":"10.1016\/j.yebeh.2017.01.024"},{"key":"key-10.14336\/AD.2021.0129-115","doi-asserted-by":"crossref","unstructured":"Puskarjov M, Seja P, Heron SE, Williams TC, Ahmad F, Iona X, et al (2014). A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. EMBO Rep, 15:723-729.","DOI":"10.1002\/embr.201438749"},{"key":"key-10.14336\/AD.2021.0129-116","doi-asserted-by":"crossref","unstructured":"Malmgren K, Thom M (2012). Hippocampal sclerosis--origins and imaging. Epilepsia, 53 Suppl 4:19-33.","DOI":"10.1111\/j.1528-1167.2012.03610.x"},{"key":"key-10.14336\/AD.2021.0129-117","doi-asserted-by":"crossref","unstructured":"Cavarsan CF, Malheiros J, Hamani C, Najm I, Covolan L (2018). Is Mossy Fiber Sprouting a Potential Therapeutic Target for Epilepsy? Front Neurol, 9:1023.","DOI":"10.3389\/fneur.2018.01023"},{"key":"key-10.14336\/AD.2021.0129-118","doi-asserted-by":"crossref","unstructured":"Muzumdar D, Patil M, Goel A, Ravat S, Sawant N, Shah U (2016). Mesial temporal lobe epilepsy - An overview of surgical techniques. Int J Surg, 36:411-419.","DOI":"10.1016\/j.ijsu.2016.10.027"},{"key":"key-10.14336\/AD.2021.0129-119","doi-asserted-by":"crossref","unstructured":"Kadam SD, Dudek FE (2007). Neuropathogical features of a rat model for perinatal hypoxic-ischemic encephalopathy with associated epilepsy. J Comp Neurol, 505:716-737.","DOI":"10.1002\/cne.21533"},{"key":"key-10.14336\/AD.2021.0129-120","doi-asserted-by":"crossref","unstructured":"Hampel P, R\u00f6mermann K, Gailus B, Johne M, Gericke B, Kaczmarek E, et al (2021). Effects of the NKCC1 inhibitors bumetanide, azosemide, and torasemide alone or in combination with phenobarbital on seizure threshold in epileptic and nonepileptic mice. Neuropharmacology, 185:108449.","DOI":"10.1016\/j.neuropharm.2021.108449"},{"key":"key-10.14336\/AD.2021.0129-121","doi-asserted-by":"crossref","unstructured":"Baud MO, Kleen JK, Mirro EA, Andrechak JC, King-Stephens D, Chang EF, et al (2018). Multi-day rhythms modulate seizure risk in epilepsy. Nature Communications, 9:88.","DOI":"10.1038\/s41467-017-02577-y"},{"key":"key-10.14336\/AD.2021.0129-122","doi-asserted-by":"crossref","unstructured":"Ulate-Campos A, Tsuboyama M, Loddenkemper T (2017). Devices for Ambulatory Monitoring of Sleep-Associated Disorders in Children with Neurological Diseases. Children (Basel). doi: .","DOI":"10.3390\/children5010003"},{"key":"key-10.14336\/AD.2021.0129-123","doi-asserted-by":"crossref","unstructured":"Helmstaedter C, Elger CE (2009). Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease? Brain, 132:2822-2830.","DOI":"10.1093\/brain\/awp182"},{"key":"key-10.14336\/AD.2021.0129-124","doi-asserted-by":"crossref","unstructured":"Boylan GB, Stevenson NJ, Vanhatalo S (2013). Monitoring neonatal seizures. SeminFetal Neonatal Med, 18:202-208.","DOI":"10.1016\/j.siny.2013.04.004"}],"container-title":["Aging and disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.aginganddisease.org\/fileup\/2152-5250\/PDF\/ad-0-0-0-2103221510-1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T01:30:56Z","timestamp":1627522256000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2021.0129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":124,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.14336\/ad.2021.0129","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"print"}],"subject":[],"published":{"date-parts":[[2021]]}}}