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This study aimed to evaluate for disease modifying effects of sodium selenate treatment in the chronically epileptic rat post-status epilepticus (SE) model of drug-resistant TLE. Wistar rats underwent kainic acid-induced SE or sham. Ten-weeks post-SE, animals received sodium selenate, levetiracetam, or vehicle subcutaneousinfusion continuously for 4 weeks. To evaluate the effects of the treatments, one week of continuous video-EEG was acquired before, during, and 4, 8 weeks post-treatment, followed by behavioral tests. Targeted and untargeted proteomics and metabolomics were performed on post-mortem brain tissue to identify potential pathways associated with modified disease outcomes. Telomere length was investigated as a novel surrogate marker of epilepsy disease severity in our current study. The results showed that sodium selenate treatment was associated with mitigation of measures of disease severity at 8 weeks post-treatment cessation; reducing the number of spontaneous seizures (p&lt; 0.05), cognitive dysfunction (p&lt; 0.05), and sensorimotor deficits (p&lt; 0.01). Moreover, selenate treatment was associated with increased protein phosphatase 2A (PP2A) expression, reduced hyperphosphorylated tau, and reversed telomere length shortening (p&lt; 0.05). Network medicine integration of multi-omics\/pre-clinical outcomes identified protein-metabolite modules positively correlated with TLE. Our results provide evidence that treatment with sodium selenate results in a sustained disease-modifying effect in chronically epileptic rats in the post-KA SE model of TLE, including improved comorbid learning and memory deficits.<\/jats:p>","DOI":"10.7554\/elife.78877","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T07:15:17Z","timestamp":1678346117000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.78877","source":"Crossref","is-referenced-by-count":35,"title":["Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-9415","authenticated-orcid":true,"given":"Pablo M","family":"Casillas-Espinosa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, The Royal Melbourne Hospital, The University of 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