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抗癫痫药物对轴突再髓鞘化的影响:苯妥英钠、左乙拉西坦、卡马西平和丙戊酸在创伤性脑损伤后的应用。

The effect of antiepileptic drugs on re-myelinization of axons: Phenytoin, levetiracetam, carbamazepine, and valproic acid, used following traumatic brain injury.

机构信息

Department of Neurosurgery,Ankara Yildirim Beyazit University Faculty of Medicine, Department of Neurosurgery, Ankara, Turkey.

Department of Neurosurgery, University of Health Sciences, Gülhane Faculty of Medicine, Ankara, Turkey.

出版信息

Clin Neurol Neurosurg. 2021 Oct;209:106911. doi: 10.1016/j.clineuro.2021.106911. Epub 2021 Aug 31.

Abstract

OBJECTIVE

Traumatic brain injury is a major health and socioeconomic problem and the first cause of young death worldwide. For this reason, the prevention of post-traumatic brain injury and the research of new methods for it are important today. In this study, we aimed to determine whether the use of antiepileptic drugs contributed to axonal healing after traumatic brain injury.

METHODS

Thirty-six Long-Evans rats, each weighing 300-350 g, were used in this study. A total of 6 groups, including the sham, control, and 4 study groups, were determined. A 1.5 mm-sized trauma was created in the biparietal area with a blunt-tipped dissector. Carbamazepine phenytoin valproic acid and levetiracetam (phenytoin: 30 mg/kg, valproic acid: 60 mg/kg, levetiracetam: 80 mg/kg, and carbamazepine: 36 mg/kg) were intraperitoneally administered to the study groups, and the control group intraperitoneally received a physiological saline solution (15 ml/kg) twice daily for 3 days. After 72 h, hemispheres of the sacrificed subjects were taken for examination in biochemistry and histology. Glutathione, malondialdehyde, and NG2 levels in the samples were determined.

RESULTS

No significant difference was found in biochemical measurements. Histopathological examination revealed that the NG2 expression was more intense in the group treated with phenytoin and levetiracetam (phenytoin was partly higher) and the amount of edema decreased. The NG2 expression increased and the edema decreased, though lower in the group treated with carbamazepine and valproic acid, compared with phenytoin and levetiracetam. An increase in the NG2 expression and edema intensity were determined in the control and sham groups.

CONCLUSION

Antiepileptic drug selection after traumatic brain injury is an important medical matter. Although the patient-oriented selection is essential, the study suggests that the choice of phenytoin, levetiracetam carbamazepine, and valproic acid will, respectively, have an accelerating effect for axonal healing.

摘要

目的

外伤性脑损伤是一个主要的健康和社会经济问题,也是全球年轻人死亡的首要原因。因此,今天预防创伤性脑损伤和研究新的治疗方法非常重要。在这项研究中,我们旨在确定抗癫痫药物的使用是否有助于创伤性脑损伤后的轴突愈合。

方法

本研究使用了 36 只长耳大白鼠,体重 300-350 克。总共确定了 6 个组,包括假手术组、对照组和 4 个研究组。使用钝头解剖器在双侧顶区造成 1.5 毫米大小的创伤。将卡马西平、苯妥英钠、丙戊酸钠和左乙拉西坦(苯妥英钠:30mg/kg,丙戊酸钠:60mg/kg,左乙拉西坦:80mg/kg,卡马西平:36mg/kg)腹腔内给药至研究组,对照组腹腔内每天两次给予生理盐水(15ml/kg),共 3 天。72 小时后,处死实验动物并取半球进行生化和组织学检查。测定标本中的谷胱甘肽、丙二醛和 NG2 水平。

结果

生化测定无显著性差异。组织病理学检查显示,苯妥英钠和左乙拉西坦组(苯妥英钠部分更高)的 NG2 表达更强烈,水肿减少。与苯妥英钠和左乙拉西坦相比,卡马西平和丙戊酸钠组的 NG2 表达增加,水肿减少。对照组和假手术组的 NG2 表达增加,水肿程度加重。

结论

创伤性脑损伤后抗癫痫药物的选择是一个重要的医学问题。尽管以患者为中心的选择是必要的,但研究表明,苯妥英钠、左乙拉西坦、卡马西平和丙戊酸钠的选择将分别对轴突愈合产生加速作用。

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