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临床前评估新型杂交化合物 C11 对匹罗卡品诱导的癫痫持续状态后小鼠神经发生和认知功能的疗效。

Preclinical Assessment of a New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice.

机构信息

Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.

Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland.

出版信息

Int J Mol Sci. 2021 Mar 22;22(6):3240. doi: 10.3390/ijms22063240.

Abstract

Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The confirmed protective effect of C11 on astrocytes, as well as the demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.

摘要

癫痫持续状态(SE)是一种常见的医疗紧急情况,可导致多种神经紊乱,包括认知障碍和异常神经发生。本研究的目的是评估新型吡咯烷-2,5-二酮衍生物化合物 C11 的潜在神经保护特性,并评估 C11 和左乙拉西坦(LEV)对匹鲁卡品(PILO)诱导的 SE 后小鼠神经发生和认知功能的影响。结果表明,C11(500、1000 和 2500ng/mL)在 MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴盐)试验中对营养应激条件下的星形胶质细胞具有保护作用。在 SE 后 72 小时用 C11(20mg/kg)和 LEV(10mg/kg)治疗的 PILO 小鼠的研究中,结果表明 C11 对改善神经发生有明显的有益作用,与 PILO 对照和 PILO LEV 小鼠相比。此外,这种有益的影响反映在评估小鼠认知功能的 Morris 水迷宫测试中。C11 对星形胶质细胞的确认保护作用,以及对神经发生和认知功能的有益影响,强烈表明需要对该化合物进行进一步的先进分子研究,以确定 C11 的确切神经保护作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4459/8004689/bffcf4cfde76/ijms-22-03240-g001.jpg

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