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Resveratrol (RSV) is a polyphenol with antioxidant and anti-inflammatory properties, but its poor bioavailability limits therapeutic use. This study investigated whether PEGylated liposomes encapsulating RSV (LipRSV) could modulate oxidative and behavioral alterations in a valproic acid (VPA)-induced rat model of ASD.\u00a0PEGylated LipRSV were synthesized, characterized as hemocompatible, and administered to offspring from postnatal day (PND) 6 to 27. Behavioral tests included developmental milestones, olfactory discrimination, negative geotaxis, open field, and three-chamber social interaction. Oxidative stress markers and neurotrophins (BDNF, NGF) were quantified in the following brain regions: hippocampus, hypothalamus, striatum, cerebellum, frontal and posterior cortex.\u00a0LipRSV exerted limited and region-dependent redox effects, reducing ROS levels only in the hippocampus, cerebellum, and posterior cortex, while failing to improve behavioral outcomes and being associated with unfavorable neurochemical alterations, including reduced BDNF and NGF levels. Importantly, LipRSV also induced behavioral deficits, redox imbalance, and neurochemical alterations in control animals, indicating treatment-related effects in the absence of VPA exposure.\u00a0LipRSV modulated oxidative stress in a region-dependent manner without improving behavioral deficits in the VPA model and was associated with reduced BDNF and NGF levels. This study provides evidence that modulation of oxidative stress alone is insufficient to rescue behavioral phenotypes in the VPA model of ASD. These findings highlight the partial neurochemical efficacy and translational limitations of this formulation, suggesting the need for optimized nanocarrier design and dosing strategies in ASD pharmacotherapy.<\/jats:p>","DOI":"10.1007\/s12031-026-02574-1","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T12:13:29Z","timestamp":1785586409000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PEGylated Liposomal Resveratrol Induces Region-Specific Redox Modulation Without Behavioral or Neurotrophin Recovery in a VPA Model of Autism"],"prefix":"10.1007","volume":"76","author":[{"given":"Vict\u00f3ria Linden","family":"de Rezende","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Fernanda Pedro","family":"Ebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via da Silva","family":"Daros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiara de Aguiar","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Janu\u00e1rio","family":"Bolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germano Lapa","family":"Viana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Pelegrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"de Souza Colonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J\u00falia Ferro","family":"Spillere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giseli","family":"da Silva Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"de Sousa Anast\u00e1cio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"De-Pieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falio C\u00e9sar Claudino","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Andrez Machado","family":"de \u00c1vila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Gon\u00e7alves Dal-B\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinara Ludvig","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"2574_CR1","doi-asserted-by":"crossref","unstructured":"Aebi H (1984) [13] Catalase in vitro. pp 121\u2013126","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"2574_CR2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejphar.2018.04.008","volume":"829","author":"SF Ahmad","year":"2018","unstructured":"Ahmad SF, Ansari MA, Nadeem A et al (2018) Resveratrol attenuates pro-inflammatory cytokines and activation of JAK1-STAT3 in BTBR T+ Itpr3tf\/J autistic mice. 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