Abstract：
Cerebral ischemia is a life-threatening health concern that leads to severe neurological complications and fatalities worldwide. Although timely intervention with clot-removing agents curtails serious post-stroke neurological dysfunctions, no effective neuroprotective intervention is available for addressing post-recanalization neuroinflammation. Herein, for the first time we studied the effect of oxyberberine (OBB), a derivative of berberine, on transient middle cerebral artery occlusion (MCAO)-generated neurological consequences in Sprague-Dawley rats. The MCAO-operated rats exhibited significant somatosensory and sensorimotor dysfunctions in adhesive removal, foot fault, paw whisker, and rotarod assays at 1 and 3 days post-surgery. These MCAO-generated neurological deficits were prevented in OBB-treated (50 and 100 mg/kg) rats, and also coincided with a smaller infarct area (in 2,3,5-triphenyl tetrazolium chloride staining) and decreased neuronal death (in cresyl violet staining) in the ipsilateral hemisphere of these animals. The immunostaining of neuronal nuclear protein (NeuN) and glial-fibrillary acidic protein (GFAP) also echoes the neuroprotective nature of OBB. The increased expression of neuroinflammatory and blood-brain barrier tight junction proteins like toll-like receptor 4 (TLR4), TRAF-6, nuclear factor kappa B (NF-κB), pNF-κB, nNOS, ASC, and IKBα in the ipsilateral part of MCAO-operated rats were restored to normal following OBB treatment. We also observed the decline in plasma levels/mRNA transcription of TNF-α, IL-1β, NLRP3, IL-6, and matrix metalloproteinase-9 and increased expression of occludin and claudin in OBB-treated rats. These outcomes imply that OBB may prevent the MCAO-induced neurological consequences and neuroinflammation by interfering with TLR4 and NLRP3 signaling in rats.
摘要：
脑缺血是一种威胁生命的健康问题，在世界范围内导致严重的神经系统并发症和死亡。然而,据报道,小檗碱(BBR)在口服生物利用度低的缺血性卒中中具有神经保护作用.在这里，第一次,我们使用了羟色胺（OBB），BBR的衍生物，研究Sprague-Dawley大鼠短暂性大脑中动脉阻塞（MCAO）引起的神经保护作用。MCAO手术的大鼠在去除粘合剂时表现出明显的体感和感觉运动功能障碍，脚部故障,爪子胡须,手术后1天和3天的旋转杆测定。在OBB治疗（50和100mg/kg）的大鼠中，这些MCAO产生的神经功能缺损得到了预防，并且还伴随着较小的梗塞面积（在2,3,5-三苯基四唑氯化物染色中）和减少的神经元死亡（在甲酚紫染色中）这些动物的同侧半球。神经元核蛋白（NeuN）和神经胶质纤维酸性蛋白（GFAP）的免疫染色也与OBB的神经保护性质相呼应。神经炎症和血脑屏障紧密连接蛋白如toll样受体4（TLR4）的表达增加，TRAF-6,核因子κB(NF-κB),pNF-κB,nNOS,ASC,OBB治疗后，MCAO手术大鼠同侧部分的IKBα恢复正常。我们还观察到TNF-α的血浆水平/mRNA转录的下降，IL-1β,在OBB处理的大鼠中，NLRP3，IL-6和基质金属蛋白酶-9以及occludin和claudin的表达增加。这些结果暗示OBB可以通过干扰大鼠中的TLR4和NLRP3信号传导来预防MCAO诱导的神经后果和神经炎症。
