Aprepitant's roles in abating seizures, behavioral, and cognitive deficits in mice model of epilepsy.

Epilepsy Behav

Pharmacology Department, Faculty of Medicine, Mutah University, P.O. Box 7, Al-Karak 61710, Jordan.

Published: October 2024

AI Article Synopsis

  • Aprepitant (APR) is a drug used to treat nausea and vomiting from chemotherapy, and this study explored its effects against seizures induced by lithium pilocarpine (li-pilo) in mice, both alone and with sodium valproate (VPA).
  • The research involved five groups of male mice, evaluating how APR and VPA individually or in combination affected seizures, behavior, and cognitive skills, along with biochemical and gene expression analysis at the end.
  • The findings showed that while APR offered some protection against seizures and improved behavioral and cognitive functions, combining APR with VPA provided complete protection, significantly enhancing brain health markers and reducing inflammatory factors.

Article Abstract

Background: Aprepitant (APR), a neurokinin 1 receptor antagonist, is an approved drug for treating chemotherapy-induced nausea and vomiting.

Objectives: Investigate the beneficial roles of APR alone or in combination with sodium valproate (VPA) against lithium pilocarpine [li-pilo]-induced seizures, behavioral changes, and cognitive deficits.

Methods: Thirty male mice were divided into five groups, each containing 6. "Vehicle Group I," "Control Group II "li-pilo, " Valproate (VPA) group III (400 mg/kg/i.p.), "APR group IV, " and "Combination Group V." Videos of mice were recorded, and they were watched for episodes of spontaneous recurring seizures (SRS). Behavioral Tests were performed. At the end of the study, animal brains were taken for biochemical assays and gene expression studies.

Results: APR partially protected against SRS with partial restoration of average behavioral and standard cognitive skills associated with a significant increase in brain SOD activity and a significant decrease in MDA, IL-1β, NF-КB, and SP-3 levels in relation to the control group. Interestingly, a combination of APR with VPA in epileptic mice showed complete protection against li-pilo-induced behavioral changes and cognitive deficits, a significant increase in brain SOD activity, and a considerable decrease in MDA, IL-1β, NF-ΚB, and SP levels to normal.

Conclusion: Using APR as an adjuvant to VPA is more effective in protecting against li-pilo-induced seizures, behavioral changes, and cognitive deficits due to its antioxidant, anti-inflammatory, and NK1 antagonist effects than using APR alone as drug therapy.

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Source
http://dx.doi.org/10.1016/j.yebeh.2024.110028DOI Listing

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