Protective Effects of Amantadine on Secondary Liver Injury Following Traumatic Brain Injury in an Experimental Rat Model

Abstract

Objective Traumatic brain injury (TBI) is known to trigger systemic inflammatory responses, leading to damage in distant organs such as the liver. Amantadine (AMA), an NMDA receptor antagonist, exhibits both anti-inflammatory and neuroprotective properties. This study investigated the protective effects of AMA against liver injury secondary to TBI in a rat model. Material and Method Forty male Wistar albino rats were randomly assigned to four groups: Control, Trauma (TRA), TRA+AMA-1, and TRA+AMA-7. TBI was induced by the Marmarou weight-drop method. AMA (45 mg/kg/day, intraperitoneal) was administered for 1 and 7 days post-TBI. Liver tissues were harvested and evaluated via histopathological scoring and immunohistochemical analysis for tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon beta (IFN-β). Results TBI significantly elevated hepatic expression of pro-inflammatory cytokines (IFN-β, IL-6, TNF-α) and caused marked histological damage, including hyperemia, hemorrhage, inflammation, and necrosis. AMA treatment markedly reduced these cytokine expressions and ameliorated histopathological alterations. The TBI+AMA-7 group exhibited substantial recovery compared to the TBI group, indicating an association between amantadine treatment and reduced histopathological liver injury. Conclusion The trauma group demonstrated significantly higher histopathological liver injury scores compared with the control group. AMA treatment was associated with reduced histopathological alterations and lower immunoreactivity of pro-inflammatory cytokines compared with the untreated trauma group.

Keywords

• Amantadine
• cytokines
• histopathology
• liver inflammation
• traumatic brain injury

Supporting Institution

This work was supported by the Scientific Research Coordination Unit of Suleyman Demirel University [TSG-2024-9515].

Project Number

TSG-2024-9515

Ethical Statement

All experimental procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Ethical approval for the study was obtained from the Suleyman Demirel University Local Animal Experiments Ethics Committee (Approval No: 15.05.2025/514-05).

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