Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study


Bozdağ S., Sucu H. K., Altun Z. S., Kahraman Akkalp A., Yılmaz O., Çelikkaya D.

TURKISH NEUROSURGERY, vol.1, no.3, pp.1-10, 2024 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 1 Issue: 3
  • Publication Date: 2024
  • Doi Number: 10.5137/1019-5149.jtn.43427-23.2
  • Journal Name: TURKISH NEUROSURGERY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, MEDLINE
  • Page Numbers: pp.1-10
  • Dokuz Eylül University Affiliated: Yes

Abstract

Aim:Subarachnoid hemorrhage (SAH) is a devastating disease, resulting in imparting long-term cognitive and sensorimotor deficits. Nimodipine is the only drug that reduces the poor outcomes for SAH patients. Dexamethasone is widely employed for various purposes in SAH patients undergoing microsurgical clipping. For example, postcraniotomy cerebral edema and severe headaches have been attributed to meningeal inflammation. Furthermore, strong evidence suggests that inflammation contributes to the poor outcomes. Recently, interest in the role of inflammation in delayed cerebral ischemia (DCI) has been raised, and studies have demonstrated the beneficial effects of dexamethasone in SAH. In this direction, we aimed to understand the effects of the combination of dexamethasone and nimodipine in SAH.Material and Methods:In this study, 35 female adult Wistar Albino rats were randomly assigned to four groups: Sham (n=8), nontreatment+SAH (n=9), SAH with nimodipine (n=9, oral gavage, 12mg/kg, BID) treatment, and SAH with combined therapy with nimodipine and dexamethasone (n=9, intraperitoneally, 1mg/kg, BID). The “cisterna magna double injection of autologous blood” model was used. The animals were euthanized 5 days after the first injection. Results:Of the total, five rats died before euthanasia. The nontreatment+SAH group showed the worst score in neurological examinations, and the most severe histopathological findings were noted in terms of vasospasm. The SAH+nimodipine group showed the best neurological score and the closest histopathological results to those of the Sham group, whereas adding dexamethasone to nimodipine treatment (the SAH+nimodipine+dexamethasone group) worsened the neurological and histopathological outcomes.Conclusion:We thus concluded that the therapeutic effects of nimodipine were impaired when combined with dexamethasone. We thus hypothesized that dexamethasone possibly induces the CYP3A4-enzyme that metabolizes nimodipine. However, it should be noted that our results are based on laboratory findings obtained on a small sample, therefore further studies with drug–drug interaction on a larger sample size through CYP3A4-enzyme and clinical confirmation are warranted.