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Pourmohammadi P, Gheibi M, Baghi Keshtan S, Ghadirzadeh E, Pourhossein M, Siahposht-Khachaki A. Neuroprotective Effects of Astaxanthin After Middle Cerebral Artery Occlusion Stroke in Male Rats: The CA1 Hippocampal Region. BCN 2025; 16 (6) :1143-1158
URL: http://bcn.iums.ac.ir/article-1-3395-en.html

Introduction: 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.
Methods: 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-1β), cerebral edema, and hippocampal CA1 histology were analyzed.
Results: 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-1β 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.
Conclusion: Post-ischemic ATX administration provides neuroprotection in a rat MCAO model, with 25–50 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.