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Excessive levels of glutamate and insufficient levels of inhibitory GABA are involved in its pathophysiology. Valproic acid (Val), a GABAergic agonist, is one of the first\u2010line antiepileptic drugs, but it shows many adverse side effects at the clinical dose. Clavulanic acid (CA), a \u03b2\u2010lactamase inhibitor, has been demonstrated to increase glutamate transporter\u20101 expression. This study evaluated the effects of CA and Val in an epilepsy rat model. Male Wistar rats received intraperitoneal injections of pentylenetetrazol (PTZ, 35\u2009mg\/kg, every other day, IP, for 13\u2009days) to induce kindling epilepsy. After four times of PTZ injection, rats received daily treatment with CA (1 or 10\u2009mg\/kg, IP), Val (50 or 100\u2009mg\/kg, IP), or the combination of CA (1\u2009mg\/kg) and Val (50\u2009mg\/kg) for 7 consecutive days. Motor, learning, and memory functions were measured. Rats with PTZ\u2010induced kindling exhibited seizures, motor dysfunction, cognitive impairment, and cell loss and reduction of neurogenesis in the hippocampus. Neither 1\u2009mg\/kg CA nor 50\u2009mg\/kg Val treatment was effective in alleviating behavioral and neuronal deficits. However, treatment with 10\u2009mg\/kg CA, 100\u2009mg\/kg Val, and the combination of 1\u2009mg\/kg CA and 50\u2009mg\/kg Val improved these behavioral and neuronal deficits. Particularly, the combination of CA and Val showed synergistic effects on seizure suppression, suggesting the potential for treating epilepsy and related neuronal damage and motor and cognitive deficits.<\/jats:p>","DOI":"10.1111\/fcp.12729","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T06:18:50Z","timestamp":1632205130000},"page":"1032-1044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Treatment with the combination of clavulanic acid and valproic acid led to recovery of neuronal and behavioral deficits in an epilepsy rat model"],"prefix":"10.1111","volume":"35","author":[{"given":"Chiung\u2010Hui","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Chung Shan Medical University  Taichung 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