Dexmedetomidine (DEX) is a selective alpha-2 adrenergic receptor agonist with sedative and anxiolytic properties. Increasing evidence reports that DEX has a neuroprotective effect. In this study, we investigated the potential effects of DEX on learning and memory functions in rats with experimental cognitive impairment. In the study, 21 adult male rats were used. The rats were divided into three groups, namely control, Scopolamine (SCOP) and SCOP + DEX. Cognitive impairment was induced with 1 mg/kg SCOP daily for 21 days. DEX was administered at a dose of 10 µg/kg between days 14 and 21 of the experiment. Following the injections, a spatial memory test was performed with a Morris Water Maze (MWM). At the end of the experiment, the hippocampus was dissected. The brain-derived neurotrophic factor (BDNF), acetylcholine (ACh) and acetylcholinesterase (AChE) levels were determined by ELISA. The tropomyosin receptor kinase B (TrkB) and Cyclic AMP-Response Element-Binding Protein (CREB) levels were measured by immunohistochemistry. DEX treatment improved the learning performance of rats compared to SCOP for 5 days. However, it did not significantly change memory performance. DEX increased the BDNF and ACh levels in the hippocampus while decreasing the AChE levels. Similarly, DEX treatment significantly increased CREB phosphorylation. No significant difference was observed between the TrkB receptor levels of the groups. This study demonstrated that the role of DEX in reducing SCOP-induced cognitive impairment is partially mediated by the increase in BDNF/TrkB/CREB signaling pathway activity.

Background and Objectives: Hind limb ischemia–reperfusion (I/R) injury is a serious clinical condition that requires urgent treatment and develops as a result of a sudden decrease in blood flow in the extremity. Antioxidant combinations are frequently used in diseases today. This study aimed to investigate and compare the effectiveness of ellagic acid (EA) and berberine (BER), which are important antioxidants, and the combination on hind limb I/R injury to evaluate their therapeutic power. Materials and Methods: Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham, I/R, EA+I/R, BER+I/R, and EA/BER+I/R. In the I/R procedure, the infrarenal abdominal aorta was clamped and reperfused for 2 h. EA (100 mg/kg, ip) and BER (200 mg/kg, ip) were administered in the 75th minute of ischemia. Oxidative stress markers (MDA, GSH, SOD, and CAT) and TNF-α were measured. Apoptosis (Bax, Bcl-2, and Cleaved caspase-3) and pyroptosis (Nrf2, NLRP3, and Gasdermin D) pathways were evaluated via Western blot. Muscle tissue was examined histopathologically by hematoxylin eosin staining. One-way ANOVA and post hoc LSD tests were applied for statistical analyses (p < 0.05). Results: Bax levels increased in the ischemia group and decreased with EA and BER (p < 0.05). Bcl-2 levels decreased in the ischemia group but increased with EA and BER (p < 0.05). The highest level of the Bax/Bcl-2 ratio was in the I/R group (p < 0.05). Cleaved caspase 3 was higher in the other groups compared to the sham group (p < 0.05). While Nrf2 decreased in the I/R group, NLRP3 and Gasdermin D increased; EA and BER normalized these levels (p < 0.05). In the histopathological analysis, a combination of EA and BER reduced damage (p < 0.05). TNF-α levels were similar between groups (p > 0.05). MDA levels were reduced by EA and BER, but GSH, SOD, and CAT levels were increased (p < 0.05). Conclusions: It was concluded that TNF-α levels depend on the degree and duration of inflammation and that no difference was found in relation to duration in this study. As a result, EA, BER, and their combination could be potential treatment agents on hind limb I/R injury with these positive effects.

Objective: The antidepressant agomelatine agent is a melatonin receptor (MT1 and MT2) agonist and a serotonin receptor (5-HT2C) antagonist. Increasing evidence shows that agomelatine has neuroprotective and neuromodulatory effects. In this study, the potential effects of agomelatine in rats with scopolamine-induced cognitive impairment were investigated.Materials and Methods: Adult male rats were administered scopolamine (1 mg/kg) and agomelatine (40 mg/kg) for 21 days. After drug administration, rats were subjected to new object recognition (NOR) and Morris water maze (MWM) tests in order to evaluate cognitive behaviors. In addition, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in the hippocampus and prefrontal cortex were evaluated.Results: Scopolamine significantly decreased both spatial memory and discrimination index (p0.05). In addition, agomelatine significantly increased BDNF levels in both hippocampus and prefrontal cortex compared to the scopolamine group (p<0.05, p0.05).Conclusion: Taken together, these results demonstrated that agomelatine plays a important role in alleviating scopolamine-induced memory impairment. Therefore, we suggest that agomelatine may be a potential agent in the prevention of cognitive impairment.