背景：氨甲环酸在围术期血液保护抗纤溶策略中发挥着核心作用，但其存在可能诱发癫痫的风险，给患者带来极大痛苦，严重影响临床预后。因此，探索氨甲环酸相关癫痫成为亟待解决的重要科学问题。本研究旨在构建一种在体氨甲环酸诱发癫痫动物模型，从行为学、脑电图、组织学和代谢组学多个层面对模型进行验证，并基于此模型初步探索氨甲环酸相关癫痫的潜在机制。

材料和方法：本实验选用 42 只成年健康雄性 C57BL/6J 小鼠，随机分为 7 个剂量组，每组 6 只。通过脑室内注射，分别给予 2μl 不同浓度的氨甲环酸，浓度梯度为对照组、1μg/μl、5μg/μl、7.5μg/μl、10μg/μl、25μg/μl、50μg/μl。以 Racine 评分标准进行行为学观察，并开展浓度剂量滴定，旨在筛选出能稳定诱发癫痫的阈浓度剂量。在确定阈浓度剂量后，另选 8 只小鼠作为氨甲环酸癫痫模型组，5 只小鼠作为对照组，采用立体定向技术为小鼠植入电极及给药导管，给药后进行连续视频 -脑电图监测以验证癫痫发作。同时，从额外的 10 只氨甲环酸癫痫小鼠和 9 只对照小鼠的海马组织中取样，用于后续 H&E 染色及尼氏染色的病理组织学评估以及非靶向超高效液相色谱组学分析。

结果：Racine行为学观察评分显示，全面癫痫发作与氨甲环酸脑室内注射的浓度梯度呈剂量依赖性关系（R=1.1127, p<0.01）。脑室注射 2μl 浓度为 7.5μg/μl 的氨甲环酸可诱发强烈的癫痫行为发作并伴随典型的癫痫棘波脑电放电，因此被确立为氨甲环酸动物癫痫模型的目标方案。相较于对照组，癫痫小鼠海马 CA3 区出现神经元坏死、神经元缺失及含有尼氏小体神经元的减少（p<0.01）。此外，代谢组学揭示多种与癫痫发作相关的代谢通路受到干扰，包括氨基酸、能量代谢，抗氧化应激代谢及神经信号调节等。

结论：本研究建立了一种明确的氨甲环酸诱发癫痫模型，该模型在海马结构和生物合成方面表现出特异性和确定性的改变，代谢组学初步分析提示多种异常代谢，包括氨基酸代谢、能量代谢和抗氧化代谢等，为研究氨甲环酸相关癫痫的潜在机制提供了重要线索，未来可基于此模型进一步深入探讨具体机制及针对性干预措施。

Background: Tranexamic acid (TXA) plays a central role in perioperative blood conservation and antifibrinolytic strategies. However, its potential to induce seizures poses significant risks, which might inflict great suffering on patients and severely impact clinical outcomes. Therefore, in-depth exploration of TXA-associated seizure is a critical scientifical issue that urgently needs to be addressed. The aim of the study was to develop an in vivo TXA-induced seizure (TIS) model, validate its features through behavioral, electroencephalograph (EEG), histological and metabolomic analyses, and preliminarily explore potential mechanisms of TXA-associated seizures. Materials and Methods: Adult healthy male C57BL/6J mice (n=42) were randomized into seven dosage groups to receive intracerebroventricular injection of TXA (vehicle, 1, 5, 7.5, 10, 25, 50 μg/μl, n=6 each). The dose titration was based on behavioral observation according to the Racine scale to identify the threshold dose regime. Further, continuous video-EEG was performed in another 8 TIS mice and 5 control mice with the stereotaxic implantation of electrodes and guide cannulas to validate seizure activity. Then hippocampus samples were obtained from additional 10 TIS mice and 9 control mice for histopathological evaluation using H&E staining and Nissl staining, as well as untargeted ultra-high-performance liquid chromatography (UHPLC)-based metabolomic analysis. Results: Racine behavioral observation revealed dose-dependent relationship between generalized seizures and the intraventricular gradient of the agent (R=1.1127, p=0.01). A dose of 2μl 7.5μg/μl TXA i.c.v. was confirmed as the target scheme to establish the model with intense behavioral seizures and typical spike epileptic EEG discharges. Histological exploration illustrated necrosis and loss of neurons as well as loss of Nissl-positive neurons (p<0.01) in the CA3 area of hippocampus. Additionally, metabolomic analysis revealed a variety of disturbed metabolic pathways related to seizures including amino acid, energy, antioxidant stress metabolism and nerve signal regulation. Conclusions: The study established a simple and explicit TXA-induced seizure model with certain and specific changes in both hippocampus structure and biosynthesis. Metabolomic analysis revealed abnormalities in amino acid, energy, and antioxidant metabolism, offering insights into potential mechanisms of TXA-associated seizures. This model provides a foundation for further mechanistic exploration and targeted interventions to ensure safe clinical use of TXA.