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We aimed to establish and characterize a novel MTLE with hippocampal sclerosis (HS) model by selective ablation of these neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using AAV vectors (flex\u2010DTA or DIO\u2010taCasp3\u2010TEVp), we performed unilateral, partial ablation of GABAergic neurons in the dentate gyrus (DG) or CA1 subregions of VGAT\u2010Cre mice. Spontaneous recurrent seizures (SRS) were monitored by video\u2010EEG. Behavioral tests and histopathological analyses were conducted to assess comorbidities and HS features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DG\u2010ablated mice all developed SRS, whereas 50%\u201370% of CA1\u2010ablated mice did. Lethal SRS occurred in around 50% of DG\u2010ablated mice. Both ablation models exhibited sustained SRS from Days 8\u201328, distinct from kainic acid model severity in some parameters. The model recapitulated anxiety\u2010like behaviors, cognitive deficits, and hallmark HS pathology including gliosis, granule cell dispersion, and mossy fiber sprouting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Selective unilateral hippocampal GABAergic interneuron loss is sufficient to drive chronic epilepsy with HS. This model provides direct causal evidence and a precise platform for investigating MTLE\u2010HS mechanisms and therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70772","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:12:02Z","timestamp":1769854322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ablation of Unilateral Hippocampal GABAergic Neurons: A Novel Mouse Model of Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-4023","authenticated-orcid":false,"given":"Ting","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery Children's Hospital of Nanjing Medical University  Nanjing 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