Abstract：
Cerebrolysin, an endogenous peptide with neuroprotective and neurotrophic properties, indicated to be beneficial on diabetic neuropathy by preliminary clinical and experimental studies but without evidence on central or peripheral action. Dorsal root ganglion (DRG) neurons, based on involvement of pain sensation in both health and disease as first relay centers for transmission and processing of peripheral nociceptive sensory signals, was used to investigate possible effects of Cerebrolysin on high glucose-induced neuropathy, as model. DRG\'s were obtained from adult rats and the isolated neurons were seeded on E-Plate®\'s equipped with gold microelectrodes, and incubated in culture media in a CO2 incubator at 37 C. DRGs were exposed to high glucose (50 mM) in the absence and presence of different concentrations of Cerebrolysin ® (2-40 mg/ml). Cell index (derived from cell viability and neurite outgrowth) was recorded with Real-Time Cell Analyzer and was used as primary outcome measure. High glucose-induced cellular neuropathy and neuroprotective effects of Cerebrolysin was evaluated from area under the curve (AUC) of cell index-time graphs. Exposure of DRG neurons to high glucose caused a rapid and persistent decrease in the mean AUC values compared to normoglycemic controls. Co-treatment with Cerebrolysin (40 mg/ml) attenuated this high glucose-induced effect in a concentration-dependent manner. In normoglycemic conditions, treatment with Cerebrolysin caused a dose-dependent increase in the mean AUC values. Cerebrolysin treatment resulted in maintenance of the functional integrity, survival, and promotion of neurite outgrowth of the cultured DRG neurons exposed to high glucose, indicating involvement of peripheral sensory neurons.
摘要：
脑活素,一种具有神经保护和神经营养特性的内源性肽，通过初步的临床和实验研究表明对糖尿病神经病变有益，但没有中枢或外周作用的证据。背根神经节（DRG）神经元，基于疼痛感觉在健康和疾病中的参与，作为传递和处理外周伤害性感觉信号的第一中继中心，用于研究脑活素对高糖诱导的神经病变的可能影响，作为模型。从成年大鼠获得DRG，并将分离的神经元接种在配有金微电极的E-Plate®上，在37°C下在CO2培养箱中在培养基中孵育。在不存在和存在不同浓度的Cerebrolysin®(2-40mg/ml)的情况下,将DRG暴露于高葡萄糖(50mM)。用实时细胞分析仪记录细胞指数(源自细胞活力和神经突生长),并用作主要结果测量。从细胞指数-时间图的曲线下面积（AUC）评估高糖诱导的细胞神经病和脑活素的神经保护作用。与正常血糖对照相比，DRG神经元暴露于高糖导致平均AUC值快速持续降低。与Cerebrolysin（40mg/ml）的共治疗以浓度依赖性方式减弱了这种高葡萄糖诱导的作用。在血糖正常的情况下，脑活素治疗导致平均AUC值的剂量依赖性增加。脑活素治疗导致功能完整性的维持，生存,并促进暴露于高糖的培养的DRG神经元的神经突生长，表明周围感觉神经元的参与。
