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Targeting these cascades may provide disease\u2010modifying treatments for TLE patients. Janus Kinase\/Signal Transducer and Activator of Transcription (JAK\/STAT) inhibitors have emerged as potential disease\u2010modifying therapies; a more detailed understanding of JAK\/STAT participation in epileptogenic responses is required, however, to increase the therapeutic efficacy and reduce adverse effects associated with global inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a mouse line in which tamoxifen treatment conditionally abolishes STAT3 signaling from forebrain excitatory neurons (nSTAT3KO). Seizure frequency (continuous in vivo electroencephalography) and memory (contextual fear conditioning and motor learning) were analyzed in wild\u2010type and nSTAT3KO mice after intrahippocampal kainate (IHKA) injection as a model of TLE. Hippocampal RNA was obtained 24\u2009h after IHKA and subjected to deep sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Selective STAT3 knock\u2010out in excitatory neurons reduced seizure progression and hippocampal memory deficits without reducing the extent of cell death or mossy fiber sprouting induced by IHKA injection. Gene expression was rescued in major networks associated with response to brain injury, neuronal plasticity, and learning and memory. We also provide the first evidence that neuronal STAT3 may directly influence brain inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Inhibiting neuronal STAT3 signaling improved outcomes in an animal model of TLE, prevented progression of seizures and cognitive co\u2010morbidities while rescuing pathogenic changes in gene expression of major networks associated with epileptogenesis. Specifically targeting neuronal STAT3 may be an effective disease\u2010modifying strategy for TLE. ANN NEUROL 2023;94:106\u2013122<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26644","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T23:03:50Z","timestamp":1679267030000},"page":"106-122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Selective Neuronal Knockout of\n                    <scp>STAT3<\/scp>\n                    Function Inhibits Epilepsy Progression, Improves Cognition, and Restores Dysregulated Gene Networks in a Temporal Lobe Epilepsy Model"],"prefix":"10.1002","volume":"94","author":[{"given":"Allison E.","family":"Tipton","sequence":"first","affiliation":[{"name":"Graduate Program for Neuroscience, Center for Systems Neuroscience Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Cruz Del Angel","sequence":"additional","affiliation":[{"name":"Department of Neurology 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