左乙拉西坦对新生儿缺氧缺血性脑损伤大鼠有神经保护作用吗？

Is levetiracetam neuroprotective in neonatal rats with hypoxic ischemic brain injury?

作者信息

Celik Y, Resitoglu B, Komur M, Polat A, Arslankoylu A E, Okuyaz C, Erdogan S, Beydagi H

出版信息

Bratisl Lek Listy. 2016;117(12):730-733. doi: 10.4149/BLL_2016_140.

DOI:10.4149/BLL_2016_140

PMID:28127971

Abstract

BACKGROUND

The aim of this study was to determine if levetiracetam (LEV) is neuroprotective in neonatal rats with hypoxic-ischemic brain injury (HIBI).

METHODS

The study included 7-d-old male Wistar rats that were randomly divided into the LEV400, LEV800, control, and sham groups. All the rats, except those in the sham group, underwent ligation of the carotid artery and were then kept in a hypoxic chamber containing 8% oxygen for 2 h. At the end of the hypoxic period the rats in the control group were administered saline solution 0.5 mL, the rats in the LEV400 group were administered LEV 400 mg.kg-1, and rats in the LEV800 group were administered LEV 800 mg.kg-1 via the intraperitoneal route. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method was used to evaluate neuronal apoptosis in the rats. The Morris Water Maze (MWM) test was performed at age 14 weeks in order to evaluate cognitive function.

RESULTS

The number of apoptotic neurons in the right hemispheres was significantly lower in the sham, LEV400, and LEV800 groups than in the control group (p < 0.001, p < 0.001, and p < 0.001, respectively). In addition, the number of apoptotic neurons in the right hemispheres was significantly lower in the LEV800 group than in the LEV400 group (p = 0.001). Platform finding time (PFT) during MWM testing was significantly shorter in the sham and LEV800 groups on d 4 than on d 1 (p = 0.001 and p = 0.006, respectively); however, PFT did not significantly change between d 1 and d 4 in the control or LEV400 groups (p = 0.91 and p = 0.096, respectively).

CONCLUSION

Based on the present findings, LEV exhibited a dose-dependent neuroprotective effect in neonatal rats with HIBI (Ref. 27).

摘要

背景

本研究的目的是确定左乙拉西坦（LEV）对缺氧缺血性脑损伤（HIBI）新生大鼠是否具有神经保护作用。

方法

该研究纳入7日龄雄性Wistar大鼠，随机分为LEV400组、LEV800组、对照组和假手术组。除假手术组大鼠外，其余大鼠均行颈动脉结扎术，然后置于含8%氧气的缺氧箱中2小时。缺氧期结束时，对照组大鼠腹腔注射0.5 mL生理盐水，LEV400组大鼠腹腔注射LEV 400 mg·kg-1，LEV800组大鼠腹腔注射LEV 800 mg·kg-1。采用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）法评估大鼠神经元凋亡情况。在14周龄时进行莫里斯水迷宫（MWM）试验以评估认知功能。

结果

假手术组、LEV400组和LEV800组右侧半球凋亡神经元数量均显著低于对照组（分别为p < 0.001、p < 0.001和p < 0.001）。此外，LEV800组右侧半球凋亡神经元数量显著低于LEV400组（p = 0.001）。MWM试验中，假手术组和LEV800组在第4天的平台寻找时间（PFT）显著短于第1天（分别为p = 0.001和p = 0.006）；然而，对照组和LEV400组在第1天和第4天之间PFT无显著变化（分别为p = 0.91和p = 0.096）。