ABSTRACT
Objective To investigate the potential effect and mechanism of curcumin in inhibiting synaptic injury in the cortex of rats with cerebral ischemia-reperfusion. Methods Sprague-Dawley rats were divided into sham-operated group, model group, low-dose curcumin (50 mg/kg) group, and high-dose curcumin (100 mg/kg) group. A model of middle cerebral artery occlusion for 2 hours and reperfusion for 24 hours was constructed, and curcumin was administered. Based on the neurological function score, the effects of curcumin on cerebral infarct volume, synaptic ultrastructure changes, inflammatory cell infiltration, and the expression of NLRP3, Caspase-1, Synapsin1, and CAMKⅡ were observed after the end of the animal treatment. Results The neurological function scores were 0, 3.25±0.43, 2.50±0.50, and 1.50±0.50 for the sham-operated group, model group, low-dose curcumin group, and high-dose curcumin group, respectively. The percentage of cerebral infarct volume was 0, (38.89±2.21)%, (33.48±1.77)%, and (23.69±2.19)%, respectively. Compared with the sham operation group, the model group had severe synaptic ultrastructure damage, extensive inflammatory cell infiltration, significantly increased expression of Caspase-1 and NLRP3 (P < 0.5), and significantly decreased expression of Synapsin1 and CAMKⅡ (P < 0.5). Curcumin treatment significantly inhibited synaptic damage, reduced inflammatory cell infiltration, decreased the expression of Caspase-1 and NLRP3 (P < 0.5), and increased the expression of Synapsin1 and CAMKII (P < 0.5), when compared with the model group. Conclusion Ischemia-reperfusion-mediated synaptic injury in rat brain triggers an inflammatory response in cortical nerve cells, and curcumin alleviates synaptic damage and reduces brain injury by inhibiting inflammatory factor levels.
ABSTRACT
OBJECTIVE To observe the effect of baicalin on Aβ25-35 induced learning and memory deficits and changes in autophagy-related genes in mice so as to explore the related mechanisms of Alzheimer disease (AD) treatment . METHODS C57 mice were administered with 3μL Aβ25-35 3 mmol·L-1 by intracerebroventricular injection to establish an AD model. Baicalin was given by intracerebroventricular injection at the dose of 25, 50 and 100 mg · kg-1 for 15 d, respectively. The total distance and the central grid residence time were measured in the open-field test. The escape latency and the time to reach the platform were monitored in the Morris water maze trial. The autophagic vacuoles in the hippocampus of the mice were observed by transmission electron microscopy before the protein expressions of microtu?bule-associated protein 1 light chain 3 (LC3) and Beclin1 in brain tissue were analyzed by Western blot?ting assay. RESULTS Intracerebroventricular injection of Aβ25-35 could reduce the total distance from (3984±321)cm to (2790±306)cm and extend central grid residence time from (3.6±1.2)s to (8.8±2.9)s in the open-field test. The escape latency of water maze also increased from (22.0 ± 1.9)s to (38.8 ± 2.2)s. Autophagic vacuoles or late autophagic vacuoles and increased Beclin1 and LC3 and protein level were observed in the hippocampus after Aβ25-35 injection. Intraperitoneal injection of Baicalin 50 and 100 mg · kg-1 for fifteen consecutive days extended the total distance in open-field test to (3705 ± 337)cm and (3968 ± 448)cm, respectively, while the central grid residence time was reduced to (5.6 ± 1.8)s and (3.9±1.5)s, respectively. The total time taken to reach the platform in water maze test was reduced to (28.6± 1.9)s, (22.9 ± 1.7)s. Mitochondrial swelling, vacuolar membrane structure or autophagic vacuoles were visible in the hippocampus. LC3 and Beclin1 protein expression was significantly up-regulated(P<0.01). CONCLUSION Baicalin shows protective effect against Aβ25-35 induced learning and memory deficits, and this effect may be related to the activation of autophagy in the mouse hippocampus.