{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:31:45Z","timestamp":1785537105466,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PIQ-PHARMA Company"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oxidative stress and membrane damage are believed to be principally involved in the pathogenesis of epilepsy. This study aimed to assess the effects of phenosanic acid (PA), an antioxidant and membrane protector, in acute pentylenetetrazole and chronic lithium\u2013pilocarpine seizure models in male Wistar rats. PA was administered acutely (ip, 120 mg\/kg BW ip, or 240 mg\/kg BW per os) or chronically (80 mg\/kg BW\/day per os). Indices of free radical oxidation, the hypothalamo\u2013pituitary\u2013adrenocortical axis, and the nitrergic system were assessed in blood and brain regions. Morphological analysis of the hippocampus was performed in the lithium\u2013pilocarpine model. PA exerted an acute anti-seizure effect in the pentylenetetrazole model. In the lithium\u2013pilocarpine model, acute PA treatment decreased the death rate and corticosterone levels in the neocortex and brainstem. In contrast, the level of free radical oxidation products reacting with thiobarbituric acid declined in the brain stem in response to chronic PA treatment. In the lithium\u2013pilocarpine model, the neuronal density in the dentate gyrus was elevated, and the proliferating cell nuclear antigen positive (PCNA+) cell counts in the subgranular zone did not differ between groups. Doublecortin positive (DCX+) cell count was significantly increased after chronic PA treatment. PA-induced reduction in mortality in the lithium\u2013pilocarpine epilepsy model may be partially mediated by decreasing the lipid peroxidation and corticosterone levels in different brain regions. Chronic PA treatment may affect adult hippocampal neurogenesis by either prolonging the action of factors that increase neurogenesis after status epilepticus or by slowing down the neuronal differentiation rate. These data suggest that PA may be a disease-modifying AED able to hamper epileptogenesis.<\/jats:p>","DOI":"10.3390\/ijms26125668","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T03:53:12Z","timestamp":1749786792000},"page":"5668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Phenosanic Acid in Rat Seizure Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6726-142X","authenticated-orcid":false,"given":"Victor A.","family":"Aniol","sequence":"first","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia A.","family":"Lazareva","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia V.","family":"Moiseeva","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6845-0089","authenticated-orcid":false,"given":"Olga A.","family":"Nedogreeva","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita R.","family":"Novikova","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel A.","family":"Kostryukov","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Onufriev","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"},{"name":"Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 115419 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-7954","authenticated-orcid":false,"given":"Natalia V.","family":"Gulyaeva","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia"},{"name":"Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 115419 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","first-page":"641","article-title":"Stress-associated molecular and cellular hippocampal mechanisms common for epilepsy and comorbid depressive disorders","volume":"86","author":"Gulyaeva","year":"2021","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.neurol.2025.03.009","article-title":"Are antiseizure medications disease modifiers?","volume":"181","author":"Tyvaert","year":"2025","journal-title":"Rev. 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