Effects of the combination of melatonin and N-acetylcysteine on the inflammatory response in a rat model of cerebral ischemia

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-06-10 DOI:10.1016/j.ibneur.2025.06.004

Pouria Soleimani , Saied Nekoonam , Fariba Zafari , Fatemeh Sabbaghziarani

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Abstract

Stroke is the second leading cause of death and long-term damage globally. Inflammation is a significant factor in the onset of ischemic stroke. This study investigated the simultaneous administration of melatonin and N-acetylcysteine (NAC) on inflammation in rat cerebral ischemia. First, 30 male Wistar rats were randomly divided into five groups (n = 6), including the sham group without ischemia, the ischemic group, and the ischemic groups treated with NAC, melatonin, and NAC + melatonin, respectively. To induce ischemia, a silicone-coated monofilament was placed from the common carotid artery towards the middle cerebral artery and stained for 60 min. The rats were treated by administering NAC (50 mg/kg), melatonin (5 mg/kg) and the combination of NAC + melatonin by intraperitoneal injection after ischemia induction. The animals were assessed for sensory-motor activity at 24 and 72 h. Following sacrifice, the rats' brain was dissected to estimate infarct volume after triphenyltetrazolium chloride (TTC) staining. Inflammatory parameters were then analyzed through gene expression analysis using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and nucleotide oligomerization domain (NOD)-like receptor family with pyrin domain 1 and 3 (NLRP1 and NLRP3). The results showed a significant decrease in mRNA expression of the target genes in the rats treated with NAC + melatonin compared to the ischemic group (p < 0.05). The group that received the combined treatment exhibited enhanced sensory-motor function and a reduced brain infarct volume compared to the other groups (p < 0.05). In summary, the combined use of NAC and melatonin has shown promise in enhancing neurobehavioral function and decreasing the volume of cerebral infarction by regulating the inflammatory signaling pathway.

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褪黑素联合n -乙酰半胱氨酸对脑缺血大鼠模型炎症反应的影响

中风是全球造成死亡和长期损害的第二大原因。炎症是缺血性中风发病的重要因素。本研究探讨褪黑素和n -乙酰半胱氨酸（NAC）同时给药对脑缺血大鼠炎症的影响。首先，将30只雄性Wistar大鼠随机分为5组（n = 6），分别为无缺血假手术组、缺血组、NAC +褪黑素组、NAC + 褪黑素组。为了诱导缺血，从颈总动脉向大脑中动脉放置一根硅涂层单丝，染色60 min。大鼠缺血后腹腔注射NAC（50 mg/kg）、褪黑素（5 mg/kg）和NAC + 褪黑素联合治疗。在24和72 h时评估动物的感觉运动活动。牺牲后，解剖大鼠脑，三苯四唑氯（TTC）染色估计梗死体积。通过反转录定量聚合酶链反应（RT-qPCR）对核因子κB （NF-κB）、肿瘤坏死因子α (TNF-α)、白细胞介素-1β (IL-1β)和pyrin结构域1和3的核苷酸寡聚结构域（NOD）样受体家族（NLRP1和NLRP3）进行基因表达分析，分析炎症参数。结果显示，与缺血组相比，NAC + 褪黑素处理大鼠靶基因mRNA表达显著降低（p <； 0.05）。与其他组相比，接受联合治疗的组表现出增强的感觉运动功能和减少的脑梗死体积（p <； 0.05）。综上所述，NAC和褪黑激素联合使用通过调节炎症信号通路，在增强神经行为功能和减少脑梗死体积方面显示出前景。

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