{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:19:47Z","timestamp":1787674787642,"version":"build-2784847793"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Post\u2010traumatic stress disorder (PTSD) is a complicated neuropsychiatric disorder that is marked by long\u2010term neuroinflammation, oxidative stress, and poor neuroplasticity in stress\u2010sensitive brain areas. Hesperidin is a citrus\u2010derived flavanone glycoside that has been reported to have multitarget neuroprotective effects with antioxidant, anti\u2010inflammatory, and neurotrophic regulatory activities. However, its integrated effects across convergent pathological pathways in validated PTSD models remain insufficiently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were subjected to the single prolonged stress (SPS) paradigm and treated with hesperidin (50, 100, and 200\u2009mg\/kg), fluoxetine (20\u2009mg\/kg), or vehicle for 14\u2009days. Biochemical assessments (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD]) and immunohistochemical measurements of neuronal and glial integrity (NeuN, glial fibrillary acidic protein [GFAP], brain\u2010derived neurotrophic factor [BDNF]) in the hippocampus, amygdala, and prefrontal cortex were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SPS exposure induced marked oxidative imbalance, evidenced by increased MDA levels and reduced CAT activity, alongside significant upregulation of tumor necrosis factor \u03b1 (TNF\u2010\u03b1), interleukin 6 (IL\u20106), and IL\u20101\u03b2, increased astrocytic reactivity (GFAP), and reduced BDNF expression. Hesperidin treatment significantly attenuated lipid peroxidation, partially restored CAT activity, and suppressed pro\u2010inflammatory cytokines, with the most pronounced effect observed for IL\u20101\u03b2. Notably, hesperidin reduced astrocytic activation and preserved neuronal morphology, while enhancing BDNF expression in a dose\u2010dependent manner, with optimal effects at 50\u2013100\u2009mg\/kg. Conversely, there was little group variation in the activity of SOD, implying pathway\u2010selective redox regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hesperidin has multipathway, coordinated, modulatory effects on oxidative stress, neuroinflammation, glial activation, and neurotrophic signaling in the SPS model of PTSD. These findings support its utility as a mechanistic probe for interrogating convergent stress\u2010related neuropathological pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70244","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T07:54:24Z","timestamp":1786002864000},"page":"1661-1673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multipathway modulation of neuroinflammation and oxidative stress by hesperidin in a rat single prolonged stress model of post\u2010traumatic stress disorder"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-807X","authenticated-orcid":false,"given":"Godson Emeka","family":"Anyanwu","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Biomedical Sciences Kampala International University  Kampala 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