Karabacak Pınar, Bindal Ahmet, Ozcan Mustafa Soner, Ilhan Ilter, Tepebasi Muhammet Yusuf, Arlioğlu Melih, Taner Rumeysa, Asci Halil
Department of Anesthesiology and Reanimation, Suleyman Demirel University, Isparta, Türkiye.
Department of Medical Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Türkiye.
Iran J Basic Med Sci. 2025;28(5):620-626. doi: 10.22038/ijbms.2025.81436.17626.
Sepsis, a severe consequence of infection leading to organ failure, incites damage in frequently affected brain tissue through inflammation and oxidative stress. This study aimed to assess the effectiveness of amantadine, an N-methyl-D-aspartate (NMDA) receptor antagonist, in mitigating sepsis-induced brain damage.
Thirty-two Wistar albino male rats were allocated into four groups: control, LPS (lipopolysaccharide 5 mg/kg, intraperitoneal, single-dose), LPS + amantadine, and amantadine alone. Six hours post-LPS administration, rats were euthanized under anesthesia. The neutrophilic infiltration and necrosis reaction were assessed in lung tissues through histopathological analysis, while expressions of interferon-alpha (IFN-α), caspase-3 (Cas-3), and Tumor necrosis factor-alpha (TNF-α) were examined using the immunohistochemical method. Levels of biochemical total anti-oxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were evaluated via the ELISA method. IL-1β, Cas-1, NLRP3, and IL-18 were evaluated via real-time qPCR.
The LPS group exhibited histopathologically significant hyperemia, increased septal tissue thickness, hemorrhage, and inflammatory cell infiltrates, and increased IFN-α, Cas-3, TNF-α immunohistochemical expressions, and IL-1 beta, IL-18, NLRP3, and Cas-1, gene expressions compared to the control group. All these findings were significantly reversed with amantadine treatment.
The pathophysiology of brain damage due to systemic inflammation is complex. Our findings suggest that amantadine reduces neuronal injury in the brain by alleviating oxidative stress and inflammation. Notably, amantadine's efficacy appears to extend beyond NMDA receptors, implicating involvement in alternative pathways, such as Cas-1 activation by the NLRP3 inflammasome.
脓毒症是感染导致器官衰竭的严重后果，通过炎症和氧化应激对常受影响的脑组织造成损害。本研究旨在评估N-甲基-D-天冬氨酸（NMDA）受体拮抗剂金刚烷胺减轻脓毒症诱导的脑损伤的有效性。
将32只Wistar白化雄性大鼠分为四组：对照组、脂多糖（LPS，5mg/kg，腹腔注射，单剂量）组、LPS+金刚烷胺组和单独使用金刚烷胺组。给予LPS后6小时，在麻醉下对大鼠实施安乐死。通过组织病理学分析评估肺组织中的中性粒细胞浸润和坏死反应，同时采用免疫组织化学方法检测α-干扰素（IFN-α）、半胱天冬酶-3（Cas-3）和肿瘤坏死因子-α（TNF-α）的表达。通过酶联免疫吸附测定（ELISA）法评估生化总抗氧化状态（TAS）、总氧化状态（TOS）和氧化应激指数（OSI）水平。通过实时定量聚合酶链反应（qPCR）评估白细胞介素-1β（IL-1β）、半胱天冬酶-1（Cas-1）、NLR家族含pyrin结构域蛋白3（NLRP3）和白细胞介素-18（IL-18）。
与对照组相比，LPS组在组织病理学上表现出明显的充血、间隔组织厚度增加、出血和炎性细胞浸润，以及IFN-α、Cas-3、TNF-α免疫组织化学表达增加，IL-1β、IL-18、NLRP3和Cas-1基因表达增加。金刚烷胺治疗可显著逆转所有这些发现。
全身炎症导致脑损伤的病理生理学很复杂。我们的研究结果表明，金刚烷胺通过减轻氧化应激和炎症来减少脑中的神经元损伤。值得注意的是，金刚烷胺的疗效似乎超出了NMDA受体，这意味着它参与了其他途径，如NLRP3炎性小体激活Cas-1。
