Turkish Neurosurgery 2024 , Vol 34 , Num 1
Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study
Selin BOZDAG1,Hasan Kamil SUCU2,Zekiye Sultan ALTUN3,Aslı Kahraman AKKALP4,Osman YILMAZ5,Demet CELIKKAYA6
1Kastamonu Training and Research Hospital, Department of Neurosurgery, Kastamonu, Türkiye
2Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Neurosurgery, Izmir, Türkiye
3Dokuz Eylul University Faculty of Medicine, Department of Oncology, Izmir, Türkiye
4Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Pathology, Izmir, Türkiye
5Dokuz Eylul University Faculty of Medicine, Department of Laboratory Animal Science, Izmir, Türkiye
6University of Health Sciences, Izmir Tepecik Training and Research Hospital, Department of Invertentional Neuroradiology, Izmir, Türkiye
DOI : 10.5137/1019-5149.JTN.43427-23.2 AIM: To evaluate the effects of the combination of nimodipine and dexamethasone in subarachnoid hemorrhage (SAH).

MATERIAL and METHODS: In this study, 35 female adult Wistar Albino rats were randomly assigned to four groups: Sham (n=8), SAH with no treatment (n=9), SAH with nimodipine (n=9, oral gavage, 12 mg/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 SAH+Nontreatment 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. Keywords : Delayed Cerebral Ischemia, Dexamethasone, Nimodipine, Subarachnoid Hemorrhage, Vasospasm

Corresponding author : Selin BOZDAG, selin.bzdg@gmail.com