Resveratrol Improves Cognitive Function in Post-stroke Depression Rats by Repressing Inflammatory Reactions and Oxidative Stress via the Nrf2/HO-1 Pathway.

Post-stroke depression (PSD) is a prevalent mental health issue, and resveratrol (RES) has been implicated in its management. This study aimed to elucidate the impact of RES on PSD. A PSD rat model was established through middle cerebral artery occlusion and chronic unpredictable mild stress. Rats received RES via gavage, and depressive behaviors were evaluated through various measures. Cerebral infarction areas and brain tissue pathology were assessed using TTC and H&E staining. Levels of inflammatory factors (TNF-α/IL-1ß/IL-6/IL-10), neurotransmitters (ACH/DA/5-HT/BDNF), and oxidative stress-related indicators (SOD/GSH-Px/MDA), along with the total Nrf2/C-Nrf2/N-Nrf2/HO-1 proteins, were analyzed. The role of the Nrf2/HO-1 pathway was investigated by co-treating rats with RES and either an Nrf2 pathway specific inhibitor (ML385) or activator (dimethyl fumarate). PSD rats exhibited depressive behaviors, disrupted neurotransmitter levels, and oxidative stress markers. RES treatment effectively alleviated these symptoms and activated the Nrf2/HO-1 pathway in PSD rat brain tissues. Co-administration of ML385 attenuated the beneficial effects of RES in PSD rats. Altogether, RES mitigates depressive behaviors, improves cognitive dysfunction, and reduces oxidative stress and inflammatory response in PSD rats. These effects are mediated through the activation of the Nrf2/HO-1 pathway, suggesting RES as a potential therapeutic agent for PSD-related cognitive impairment.

Administration of troxerutin and cerebroprotein hydrolysate injection alleviates cerebral ischemia/reperfusion injury by down-regulating caspase molecules.

BACKGROUND: Cerebral ischemia/reperfusion injury (I/R injury) is an important pathological process for nervous system. The I/R injury usually causes cerebral hypoxia, infarct or stroke. This study aimed to evaluate effects of troxerutin and cerebroprotein hydrolysate injection (TC) on I/R injury in rat models. METHODS: Middle-cerebral artery occlusion/reperfusion (MCAO/R) rat models were established. Rats were divided into normal control (NC), MCAO/R rat model (injecting saline) and MCAO/R rats administrating with TC group (injecting with TC at concentration of 2 mL/100 g body weight). Neurological scores were evaluated with Garcia scale. Magnetic resonance imaging (MRI) was employed to observe infarct area, contralateral area and apparent diffusion coefficient (ADC) values. Cerebral infarct size was examined and visualized by staining with 2,3,5-triphenyltetrazolium chloride (TTC). Western blotting assay was used to determine caspase-1, caspase-3 and caspase-8 expression. RESULTS: The infarct size of mice in MCAO/R+TC group was smaller significantly compared to that in MCAO/R group (p<0.05). The infarct/contralateral area ratio of T2 and T2 Flair signals in MCAO/R+TC group were lower significantly compared to that in MCAO/R group (p<0.05). ADC values in MCAO/R+TC group were significantly enhanced compared to that in MCAO/R group (p<0.05). The troxerutin and cerebroprotein treatment significantly increased neurological scores compared to that in MCAO/R group (p<0.05). Troxerutin and cerebroprotein treatment significantly decreased expression of caspase-1, caspase-3, caspase-8 compared to that in MCAO/R group (p<0.05). CONCLUSION: Troxerutin and cerebroprotein administration alleviated cerebral I/R injury by down-regulating caspase molecules.