Singh Navdeep, Bansal Yashika, Bhandari Ranjana, Marwaha Lovish, Singh Raghunath, Chopra Kanwaljit, Kuhad Anurag
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, India.
Pharmacology. 2017;100(3-4):172-187. doi: 10.1159/000453580. Epub 2017 Jul 1.
Intracerebral hemorrhage (ICH) contributes to 10-15% of all strokes and is a high risk factor for morbidity and mortality as compared to other subtypes of stroke, that is, cerebral ischemia and subarachnoid hemorrhage. Oxidative stress (OS)-induced neuroinflammation and neuronal cell death contribute towards the hallmarks of ICH. Spared antioxidant levels, increased inflammatory cytokines and free radicals in ICH lead to neuronal death and exaggerate the hallmarks of ICH. Intracerebroventricular (ICV) collagenase (COL-induced neuronal cell damage and cognitive deficits form a widely recognized experimental model for ICH. Naringin (NGN), a natural antioxidant bioflavonoid, has shown potent neuroprotective effects in different neurodegenerative diseases. However, its potential is least explored in pathological conditions, such as hemorrhagic stroke. This study is aimed at exploring the protective effects of NGN against ICV-COL induced behavioral, neurological and memory deficits in rats. ICV-ICH was induced by single, unilateral intrastriatal injection of COL (1 IU in 2 µL, ICV) over 10 min. From 2nd day onwards, NGN was administered in three different doses (10, 20, and 40 mg/kg; p.o.). Animals were subjected to a battery of behavioral tests to assess behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Selitto and von Frey. Poststroke depression and memory deficits were estimated using forced swim test and Morris water maze test, respectively. Poststroke depression, neurological and cognitive deficits were mitigated dose dependently by NGN administration. NGN administration also attenuated the nitro-OS and restored tumor necrosis factor-α and endogenous antioxidant levels. Our research demonstrates that NGN has a protective effect against ICH-induced neurocognitive deficits, along with mitigation of oxido-nitrosative and inflammatory stress.
脑出血（ICH）占所有中风的10%-15%，与其他中风亚型（即脑缺血和蛛网膜下腔出血）相比，是发病和死亡的高风险因素。氧化应激（OS）诱导的神经炎症和神经元细胞死亡是ICH的特征。ICH中抗氧化水平降低、炎性细胞因子和自由基增加导致神经元死亡并加剧ICH的特征。脑室内（ICV）注射胶原酶（COL）诱导的神经元细胞损伤和认知缺陷构成了一种广泛认可的ICH实验模型。柚皮苷（NGN）是一种天然抗氧化生物黄酮，在不同的神经退行性疾病中已显示出强大的神经保护作用。然而，其在诸如出血性中风等病理状况下的潜力尚未得到充分探索。本研究旨在探讨NGN对ICV-COL诱导的大鼠行为、神经和记忆缺陷的保护作用。通过在10分钟内单次单侧纹状体内注射COL（2μL中含1 IU，ICV）诱导ICV-ICH。从第二天起，以三种不同剂量（10、20和40 mg/kg；口服）给予NGN。对动物进行一系列行为测试以评估行为变化，包括神经评分测试（圆筒试验、自发运动、翻正反射、单杠试验、前肢屈曲）、活动光度计、转棒试验、Randall Selitto试验和von Frey试验。分别使用强迫游泳试验和莫里斯水迷宫试验评估中风后抑郁和记忆缺陷。给予NGN后，中风后抑郁、神经和认知缺陷呈剂量依赖性减轻。给予NGN还减轻了硝基-OS并恢复了肿瘤坏死因子-α和内源性抗氧化剂水平。我们的研究表明，NGN对ICH诱导的神经认知缺陷具有保护作用，并能减轻氧化亚硝化和炎症应激。
