Laboratory of Neuropharmacology, Fudan University School of Pharmacy, 826 Zhang Heng Road, Pu Dong, Shanghai, 201203, China.
Department of Pharmacology, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, Ningxia, China.
Neurochem Res. 2017 Oct;42(10):2798-2813. doi: 10.1007/s11064-017-2293-x. Epub 2017 May 15.
Increasing evidence demonstrates inflammation contributes to neuronal death following cerebral ischemia. Lycium barbarum polysaccharide (LBP) has been reported to prevent scopolamine-induced cognitive and memory deficits. We recently indicated that LBP exerts neuroprotective effect against focal cerebral ischemic injury in mice via attenuating the mitochondrial apoptosis pathway. The aim of this study was to investigate the neuroprotective effects of LBP against the behavioral dysfunction induced by focal cerebral ischemia injury in mice. Following 7 successive days of pretreatment with LBP (10, 20 and 40 mg/kg) and nimodipine (4 mg/kg) by intragastric gavage, mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, cerebral blood flows, the total power of the spontaneous EEG, and morphological changes were estimated. Learning and memory ability, and motor coordination were determined by Morris water maze task, rotarod and grip test. Western blot analysis, Real-Time fluorogenic PCR assays, and immunofluorescence staining were used to examine the expression of proinflammatory mediators and activation of microglia. The present study showed that LBP pretreatment significantly enhanced regional cortical blood flow and the total power of the spontaneous EEG, improved memory and motor coordination impairments, and inhibited over-activation of microglia and astrocytes after MCAO. Further study demonstrated LBP suppressed MCAO-induced activations of P65 NF-κB and P38 MAPK, and prevented up-regulations of proinflammatory mediators in hippocampus. Our data suggest that LBP can exert functional recovery of memory and motor coordination deficits and neuroprotective effect against cerebral ischemic injury in mice.
越来越多的证据表明,炎症会导致脑缺血后神经元死亡。枸杞多糖(LBP)已被报道可预防东莨菪碱引起的认知和记忆障碍。我们最近表明,LBP 通过减轻线粒体凋亡途径对小鼠局灶性脑缺血损伤发挥神经保护作用。本研究旨在探讨 LBP 对小鼠局灶性脑缺血损伤引起的行为功能障碍的神经保护作用。连续 7 天通过灌胃给予 LBP(10、20 和 40mg/kg)和尼莫地平(4mg/kg)预处理后,小鼠进行大脑中动脉闭塞(MCAO)。再灌注后,评估脑血流、自发脑电图总功率和形态变化。通过 Morris 水迷宫任务、转棒和握力测试确定学习和记忆能力以及运动协调能力。Western blot 分析、实时荧光定量 PCR 检测和免疫荧光染色用于检测促炎介质的表达和小胶质细胞的激活。本研究表明,LBP 预处理可显著增强皮质局部血流和自发脑电图总功率,改善记忆和运动协调障碍,并抑制 MCAO 后小胶质细胞和星形胶质细胞的过度激活。进一步研究表明,LBP 抑制了 MCAO 诱导的 P65 NF-κB 和 P38 MAPK 的激活,并防止了海马中促炎介质的上调。我们的数据表明,LBP 可以发挥记忆和运动协调障碍的功能恢复和对小鼠脑缺血损伤的神经保护作用。