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The present study aimed to investigate the impact of OPC exposure on neuroinflammation via disrupting the equilibrium between pro-inflammatory (ROR\u03b3t\/STAT3\/IL-17\/IL-22) and anti-inflammatory (FOXP3\/STAT5\/IL-10) pathways. The study extended to evaluate the potential of BCG vaccination in alleviating neuroinflammation. Rats were distributed into four groups: control, malathion-intoxicated group, BCG-treated group, and scopolamine-treated group. Behavioral tests and histopathological investigations of the cerebral cortex were done. FOXP3, ROR\u03b3t, STAT3, and STAT5 were estimated using qRT-PCR. Acetylcholine (Ach), BDNF, IL-10, IL-17, IL-22, BCL2, and BAX were estimated using ELISA, whereas GFAP and IL-1\u03b2 were estimated via immunohistochemical analysis. The malathion-intoxicated group revealed higher gene expression of ROR\u03b3t and STAT3, along with lower gene expression of FOXP3 and STAT5, compared with the control group. Moreover, the concentrations of IL-17, IL-22, and BAX were higher, along with lower concentrations of BDNF, IL-10, and BCL2, compared with the control group. Furthermore, GFAP and IL-1\u03b2 showed marked positive cytoplasmic expression. However, the BCG-treated group reversed all the abovementioned findings. Collectively, the study highlights that malathion induces neuroinflammation via skewing the balance between the proinflammatory (ROR\u03b3t\/STAT3\/IL-17\/IL-22) and the antiinflammatory (FOXP3\/STAT5\/IL-10), leading to behavioral fluctations and brain\u2019s histological disruption. This imbalance resulted in cytokine production, neuronal apoptosis, and neurodegeneration. BCG administration alleviates these effects owing to its anti-inflammatory and neuroprotective effects.<\/jats:p>","DOI":"10.1007\/s00210-026-05061-x","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T09:39:06Z","timestamp":1771580346000},"page":"11609-11627","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Malathion-induced neurological alterations associated with dysregulation of ROR\u03b3t\/STAT3\/IL-17 and FOXP3\/STAT5\/IL-10 pathways: potential neuroprotective effects of BCG"],"prefix":"10.1007","volume":"399","author":[{"given":"Nora M.","family":"Aborehab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai A.","family":"Abd-Elmawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara M.","family":"Aboulmagd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa M.","family":"El-Mahdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine M.","family":"Shahine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hekmat M. 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