Department of Pharmacology, Neuropharmacology Division, ISF College of Pharmacy, Moga, Punjab, India.
Drug Chem Toxicol. 2022 Nov;45(6):2769-2779. doi: 10.1080/01480545.2021.1991195. Epub 2021 Oct 21.
Chemotherapy-induced cognitive impairment (CICI) comprises different neurological problems, including difficulty in learning new things, concentrating and making decisions that affect daily life activities. Clinical reports indicate that around 70% of cancer patients receiving chemotherapy suffer from cognitive impairment. The purpose of the present study is to examine the effects of widely used anticancer medication (Carmustine) on cognitive function using mice model and investigation of the neuroprotective effects of Cerebrolysin (CBN). Cerebrolysin (CBN) is a mixture of several neurotrophic factors and active peptides with anti-inflammatory, antioxidant, and neuroprotective actions. Our study aimed to establish a mice model of Carmustine (BCNU)-induced cognitive deficits and determine the protective effects of CBN. BCNU (10 mg/kg, i.v.) was administered to mice for 28 days, and behavioral parameters were measured on a weekly basis. CBN (44 and 88 mg/kg, i.p.) was administered daily from day 1 to 28 to BCNU treatment mice. All animals were sacrificed on day 29 and brain hippocampus tissues were used for biochemical, neuroinflammatory, neurotransmitters analysis. BCNU administration animals showed impaired cognition and memory, confirmed from behavioral analysis. Further, BCNU increased oxidative stress, inflammatory cytokines release and altered neurotransmitters concentration as compared to the control group ( < 0.01). However, mice treated with CBN (44 and 88 mg/kg, i.p.) significantly and dose-dependently improved cognitive functions, reduced oxidative stress markers, inflammatory cytokines and restored neurotransmitters concentration as compared to BCNU administered mice ( < 0.05). The finding of current study suggested that CBN could be the promising compound to reverse cognitive impairment associated with use of chemotherapy.
化疗诱导的认知障碍（CICI）包括不同的神经问题，包括学习新事物、集中注意力和做出决策的困难，这些都会影响日常生活活动。临床报告表明，约 70%接受化疗的癌症患者患有认知障碍。本研究的目的是使用小鼠模型研究广泛使用的抗癌药物（卡莫司汀）对认知功能的影响，并研究脑活素（CBN）的神经保护作用。脑活素（CBN）是几种神经营养因子和具有抗炎、抗氧化和神经保护作用的活性肽的混合物。我们的研究旨在建立卡莫司汀（BCNU）诱导的认知功能障碍小鼠模型，并确定 CBN 的保护作用。BCNU（10mg/kg，静脉注射）每周给小鼠注射一次，共 28 天，并每周测量行为参数。从第 1 天到第 28 天，每天给 BCNU 处理的小鼠腹腔内注射 CBN（44 和 88mg/kg）。所有动物于第 29 天处死，取脑海马组织进行生化、神经炎症、神经递质分析。BCNU 给药动物表现出认知和记忆受损，行为分析证实了这一点。此外，与对照组相比，BCNU 增加了氧化应激、炎症细胞因子的释放和神经递质浓度的改变（ < 0.01）。然而，与 BCNU 给药小鼠相比，腹腔内给予 CBN（44 和 88mg/kg）显著且剂量依赖性地改善了认知功能，降低了氧化应激标志物、炎症细胞因子并恢复了神经递质浓度（ < 0.05）。本研究的结果表明，CBN 可能是一种有前途的化合物，可逆转与化疗使用相关的认知障碍。
