Effects of levetiracetam on neuroprotection and oxidative stress in neonatal rats with hypoxic-ischemic brain damage

Abstract

Abstract: Objective To study the neuroprotective effect of levetiracetam (LEV) with hypoxia ischemia brain-damage (HIBD) model of neonatal rats. Methods The rats were randomly divided into three groups: model group, LEV low, medium and high concentration groups [gavage with 10, 30, 50 mg/(kg·d) LEV], with 10 rats in each, and another 10 rats in sham operation group. Twenty four hours after the last administration, HE staining was used to observe the pathological changes of rat brain, TUNEL method was used to detect the apoptosis of neurons, the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α(TNF-α), and oxidative stress factors malondialdehyde(MDA), the content and activity of superoxide dismutas (SOD) in serum were detected by ELISA, and the protein expression of caspase-3, B-cell lymphoma-2(Bcl-2), nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase(HO-1) in rat brain tissue were detected by Western blot. Results Compared with the sham operation group, the morphology of brain tissue cell in the model group were disordered, showed diffuse distribution, increased vacuolation and inflammatory infiltration, the apoptosis rate of neurons, the expression of IL-6, TNF-α, MDA in serum and caspase-3 in brain tissue were significantly higher(P＜0.05), and the expression of SOD in serum, Bcl-2, Nrf2 and HO-1 in brain tissue were significantly lower(P＜0.05); Compared with the model group, the above changes of LEV in low, medium and high concentration groups were significantly reduced(P＜0.05). Conclusions LEV can alleviate inflammatory reaction and oxidative stress, and play a neuroprotective role in HIBD newborn rats.

Key words: levetiracetam, neonatal rats, neuronal cells, oxidative stress

CLC Number:

R741

WANG Hai-bin, MEN Qing-ling, CAI Yan-li, ZHOU Wen-long, GUO Hai-zhi, CHEN Rui-xiang. Effects of levetiracetam on neuroprotection and oxidative stress in neonatal rats with hypoxic-ischemic brain damage[J]. Basic & Clinical Medicine, 2021, 41(4): 545-550.

References

[1] Li B, Concepcion K, Meng X, et al. Brain-immune interactions in perinatal hypoxic-ischemic brain injury[J]. Prog Neurobiol, 2017, 159:50-68.
[2] Mai C, Mankoo H, Wei L, et al. TRPM2 channel: a novel target for alleviating ischaemia-reperfusion, chronic cerebral hypo-perfusion and neonatal hypoxic-ischaemic brain damage[J]. J Cell Mol Med, 2020, 24:4-12.
[3] Sheikh T, Gupta P, Gowda P, et al. Hexokinase 2 and nuclear factor erythroid 2-related factor 2 transcriptionally coactivate xanthine oxidoreductase expression in stressed glioma cells[J]. J Biol Chem, 2018, 30:4767-4777.
[4] Bao B, Zhang MQ, Chen ZY, et al. Sulforaphane prevents PC12 cells from oxidative damage via the Nrf2 pathway[J]. Mol Med Rep, 2019, 19:4890-4896.
[5] Sun B, Yang S, Li S, et al. Melatonin upregulates nuclear factor erythroid-2 related factor 2 (Nrf2) and mediates mitophagy to protect against early brain injury after subarachnoid hemorrhage[J]. Med Sci Monit, 2018, 13:6422-6430.
[6] 林泽鸿, 蔡晓莹, 林广裕. 地西泮与左乙拉西坦间歇短程治疗预防热性惊厥发作的研究进展[J]. 中国小儿急救医学, 2018, 25:56-60.
[7] 战美芹, 顾燕, 李梅, 等. 褪黑素在缺氧缺血性脑损伤新生大鼠线粒体自噬中的作用[J]. 中国新生儿科杂志, 2018, 33:456-462.
[8] Yang L, Zhao H, Cui H. Treatment and new progress of neonatal hypoxic-ischemic brain damage[J]. Histol Histopathol, 2020, 3:18214-18223.
[9] Wang Q, Lv H, Lu L, et al. Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury[J]. J Matern Fetal Neonatal Med, 2019, 32:3685-3692.
[10] Imai T, Sugiyama T, Iwata S, et al. Levetiracetam, an antiepileptic drug has neuroprotective effects on intracranial hemorrhage injury[J]. Neuroscience, 2020, 11:25-33.
[11] Gurgul S, Buyukakilli B, Komur M, et al. Does levetiracetam administration prevent cardiac damage in adulthood rats following neonatal hypoxia/ischemia-induced brain injury?[J]. Medicina, 2018, 54:12-24.
[12] 雷军荣, 秦军, 牟磊, 等. 左乙拉西坦对小鼠急性脑缺血再灌注损伤的神经保护作用及机制[J]. 中国临床药理学杂志, 2018, 34:678-681.
[13] 王书玲, 侯江红, 陈团营, 等. 定痫丸加减联合左乙拉西坦治疗小儿癫痫痰火扰神证疗效及对认知功能、生活质量的影响[J]. 中国实验方剂学杂志, 2018, 24:171-176.
[14] Kume T. Therapeutic potential of the activators of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway in brain disorders[J]. Biol Pharm Bull, 2017, 40:553-556.
[15] 吴可, 赵文丽, 李月影, 等. Nrf2-ARE信号通路在左乙拉西坦抗癫痫中的作用[J]. 中国药理学通报, 2017, 33:1462-1466.