{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:57:39Z","timestamp":1790859459292,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Epilepsy is a debilitating neurological disorder that drives progressive neurodegeneration, glial activation, and disrupted neuronal signaling. Despite available therapies, drug resistance and adverse effects underscore urgent need for novel interventions. This study investigated the neuroprotective and antiepileptic efficacy of pentoxifylline (PTX), a methylated xanthine derivative with anti-inflammatory and antioxidant properties, in comparison with carbamazepine (CBZ).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were subjected to pentylenetetrazole-induced kindling to establish a chronic epilepsy model, followed by 14\u00a0days of PTX or CBZ treatment. Behavioural outcomes were assessed using Racine\u2019s seizure score, open field test, and Morris water maze test, while histopathological, immunohistochemical, and molecular analyses explored canonical and non-canonical Notch-1 signaling, glial activation, and myelin integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>PTX conferred robust neuroprotection, preserving cortical histoarchitecture. PTX attenuated canonical Notch-1 (Jagged-1\/Notch-1\/NICD-1\/HES-1\/HES-5) while enhancing non-canonical (F3\/contactin\/Deltex-1) cassettes. PTX suppressed the pro-inflammatory IL-1\u03b2, reduced glial fibrillary acidic protein and Iba-1 immuno-expression, and increased MBP levels. Functionally, these molecular and structural benefits are translated into reduced seizure severity and improvements in memory, cognition, and locomotor activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, PTX demonstrates potent antiepileptic and neuroprotective properties, accompanied by integrated modulation of canonical and non-canonical Notch-1 signaling, highlighting its translational potential as an adjunctive therapy for refractory epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag115","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:45:30Z","timestamp":1789213530000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual Notch-1 pathway regulation mitigates glial activation and preserves myelin integrity: neuroprotective and anticonvulsant actions of pentoxifylline in PTZ kindling model"],"prefix":"10.1093","volume":"78","author":[{"given":"Mennatallah H","family":"Zidan","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan S","family":"El-Abhar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesrine S","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9235-7351","authenticated-orcid":false,"given":"Suzan M","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University , Cairo 11562 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100108121221800_ref1","doi-asserted-by":"publisher","first-page":"12405","DOI":"10.3390\/ijms241512405","article-title":"Pentylenetetrazole-induced seizures are increased after kindling, exhibiting vitamin-responsive correlations to the post-seizures behavior, amino acids metabolism and key metabolic regulators in the rat brain","volume":"24","author":"Aleshin","year":"2023","journal-title":"Int J Mol 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