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


Clinical Neurology and Neurosurgery, vol.209, 2021 (Journal Indexed in SCI Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 209
  • Publication Date: 2021
  • Doi Number: 10.1016/j.clineuro.2021.106911
  • Title of Journal : Clinical Neurology and Neurosurgery
  • Keywords: Antiepileptics, Neurotrauma, Traumatic brain injury


© 2021 Elsevier B.V.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.