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The aim of the present study was to demonstrate the neuroprotective effect of recombinant human erythropoietin (rhEPO) and interferon-beta-1b (IFN-\u03b2-1b) in 3-NP-induced neurotoxicity in rats. Rats were injected with 3-NP (10\u00a0mg\/kg\/day, i.p) for 2\u00a0weeks and were divided into five subgroups; the first served as the HD group, the second received rhEPO (5000\u00a0IU\/kg\/every other day, i.p.) for 2\u00a0weeks, the third received rhEPO starting from the 5th day of 3-NP injection, the fourth received IFN-\u03b2-1b (300,000 units, every day other day, s.c) for 2\u00a0weeks, and the last received IFN-\u03b2-1b starting from the 5th day of 3-NP injection. All treatments significantly improved motor and behavior performance of rats. Moreover, all treatments markedly restored mitochondrial function as well as brain-derived neurotrophic factor level, and reduced oxidative stress biomarkers, pro-inflammatory mediators, nuclear factor kappa B expression, caspase-3, and Bax\/Bcl2 ratio in the striatum. In conclusion, the present study demonstrates the neuroprotective potential of rhEPO or IFN-\u03b2-1b on 3-NP-induced neurotoxicity in rats. Furthermore, our study suggests that activation of JAK2\/STAT3 or JAK1\/STAT3 may contribute to the neuroprotective activity of rhEPO or IFN-\u03b2-1b, respectively. We also found that early treatment with rhEPO did not confer any benefits compared with late rhEPO treatment, while early IFN-\u03b2-1b showed a marked significant benefit compared with late IFN-\u03b2-1b.<\/jats:p>","DOI":"10.1007\/s10787-022-00935-x","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T04:14:31Z","timestamp":1646540071000},"page":"667-681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Recombinant human erythropoietin and interferon-\u03b2-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK\/STAT signaling pathway"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-3658","authenticated-orcid":false,"given":"Rabab H.","family":"Sayed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira H.","family":"Ghazy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed F. 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