Abstract Cerebral Ischemia (CI) triggers excitotoxicity, oxidative stress, and inflammation, resulting in neuronal injury and, in severe cases, death. We used the 2VO model (Bilateral Common Carotid Occlusion/Reperfusion) to induce CI in rats. A single 500 mg/kg oral dose of Sulbutiamine (SUL), a noted neuroprotective and antioxidant, was administered to assess its efficacy in mitigating neuroinflammation, oxidative stress, and cognitive impairment. Elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety symptoms. The forced swim test (FST) was used to evaluate depression signs. The novel object recognition (NOR) test was used to analyze learning and memory. Hippocampal and plasma Brain-derived neurotrophic factor (BDNF), Vascular endothelial growth factor-A (VEGF-A), Hypoxia-inducible factor 1-alpha (HIF1-A), Tumour Necrosis Factor alpha (TNF-A), caspase-3, and myeloperoxidase (MPO) levels were detected with ELISA. Histopathological and immunohistochemical examinations were performed to verify neuroinflammation and neural damage. The 2VO model induced symptoms of anxiety, depression, and cognitive impairment via significant neuroinflammation and oxidative stress. SUL treatment provided neuroprotection by increasing BDNF, VEGF-A, and HIF-1α levels, reducing neuroinflammation and apoptosis through decreased TNF-α and caspase-3 levels, and mitigating oxidative stress by reducing MPO levels. Histopathological examinations revealed significantly reduced markers of neuroinflammation and tissue damage in the ST group. Also, SUL reduced the symptoms of anxiety in OF, EPM, and FST tests, diminished signs of depression in the FST test, and minimized cognitive impairment on the NOR test. Results indicate that SUL may be a promising candidate for effectively reducing neuroinflammation, oxidative stress, and cognitive impairment associated with cerebral ischemia.
Arslan et al. (2026) studied this question.