en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Ischemic stroke often results in severe neurological impairment, particularly affecting the hippocampal CA1 region, which is highly vulnerable to ischemia-reperfusion injury. Astaxanthin (ATX), a potent antioxidant carotenoid, exhibits neuroprotective, anti-inflammatory, and anti-apoptotic properties. This study aimed to investigate the effects of ATX on functional, biochemical, and histological outcomes in a focal transient middle cerebral artery occlusion (MCAO) model in rats.<br> <strong>Methods</strong>: Fifty-six male Wistar rats were randomly assigned to seven groups: Intact, sham, stroke (MCAO), solvent (0.1% dimethyl sulfoxide [DMSO]), and ATX-treated groups (25, 50, or 100 mg/kg, intraperitoneally every 12 hours for 3 days post-MCAO). Neurological function (Bederson score), motor coordination (rotarod), spatial learning (Morris water maze [MWM]), and memory retention (passive avoidance learning [PAL] using shuttle box) were assessed. Cerebrospinal fluid (CSF) cytokine levels (interleukin [IL]-10, IL-1&beta;), cerebral edema, and hippocampal CA1 histology were analyzed.<br> <strong>Results</strong>: Low (25 mg/kg) and medium (50 mg/kg) ATX doses significantly improved neurological and functional performance compared with untreated MCAO rats (P<0.01). These doses increased IL-10, reduced IL-1&beta; levels, decreased brain water content, and preserved neuronal morphology in the CA1 region. Conversely, the high dose (100 mg/kg) conferred no significant benefits. Histopathology confirmed reduced neuronal damage and apoptosis at effective doses.<br> <strong>Conclusion</strong>: Post-ischemic ATX administration provides neuroprotection in a rat MCAO model, with 25&ndash;50 mg/kg yielding optimal outcomes. The observed inverted dose-response underscores the importance of precise dosing and timing. ATX represents a promising therapeutic candidate for ischemic stroke pending further translational studies.</div> Astaxanthin (ATX), Middle cerebral artery occlusion (MCAO), Reperfusion injury, Rat, Ischemic stroke 1143 1158 http://bcn.iums.ac.ir/browse.php?a_code=A-10-7494-2&slc_lang=en&sid=1 Parsa Pourmohammadi pourmohammadiparsa@gmail.com 13700319475328460056648 0009-0005-6765-111X No Animal Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Mobina Gheibi mobinagheibi78@gmail.com 13700319475328460056649 13700319475328460056649 No Department of Laboratory Sciences, Razi Hospital, Mazandaran University of Medical Sciences, Qaemshahr, Iran. Sina Baghi Keshtan sinabk94@gmail.com 13700319475328460056650 13700319475328460056650 No School of Medicine, Birjand University of Medical Sciences, Birjand, Iran. Erfan Ghadirzadeh er.ghadirzadeh@gmail.com 13700319475328460056651 13700319475328460056651 No Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Melika Pourhossein dr.pourhossein1998@gmail.com 13700319475328460056652 0009-0007-8185-1710 No Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Ali Siahposht-Khachaki ak57n@yahoo.com 13700319475328460056653 13700319475328460056653 Yes Department of Physiology, Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.