Sulimai Nurul, Brown Jason, Lominadze David
Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA .
Biomolecules. 2025 Jan 8;15(1):80. doi: 10.3390/biom15010080.
Traumatic brain injury (TBI) is an inflammatory disease causing neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg). Earlier we found that extravasated Fg induced an increased expression of neuronal nuclear factor kappa B (NF-κB) p65. In the present study, we aimed to evaluate the effect of caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB, on Fg-induced neurodegeneration in vitro and in mice with mild-to-moderate TBI. Primary mouse brain cortical neurons were treated with Fg (0.5 or 1 mg/mL) in the presence or absence of CAPE. A cortical contusion injury -induced model of TBI in C57BL/6 mice was used. Mice were treated with CAPE for two weeks. The generation of reactive oxygen species (ROS) and neuronal viability were assessed. Mice memory was assessed using novel object recognition and contextual fear conditioning tests. The generation of ROS and viability of neurons in vitro and in the brain samples were assessed. Data showed that CAPE attenuated the Fg-induced generation of ROS and neuronal death. CAPE improved the cognitive function of the mice with TBI. The results suggest that Fg-induced generation of ROS could be a mechanism involved in cognitive impairment and that CAPE can offer protection against oxidative damage and neurodegeneration.
创伤性脑损伤（TBI）是一种导致神经退行性变的炎症性疾病。炎症的后果之一是血液中纤维蛋白原（Fg）水平升高。我们之前发现，渗出的Fg会诱导神经元核因子κB（NF-κB）p65表达增加。在本研究中，我们旨在评估NF-κB抑制剂咖啡酸苯乙酯（CAPE）对体外及轻度至中度TBI小鼠中Fg诱导的神经退行性变的影响。在有或没有CAPE的情况下，用Fg（0.5或1mg/mL）处理原代小鼠脑皮质神经元。使用C57BL/6小鼠的皮质挫伤性损伤诱导的TBI模型。小鼠用CAPE治疗两周。评估活性氧（ROS）的产生和神经元活力。使用新物体识别和情境恐惧条件测试评估小鼠记忆。评估体外和脑样本中神经元的ROS产生和活力。数据显示，CAPE减弱了Fg诱导的ROS产生和神经元死亡。CAPE改善了TBI小鼠的认知功能。结果表明，Fg诱导的ROS产生可能是参与认知障碍的一种机制，并且CAPE可以提供针对氧化损伤和神经退行性变的保护作用。
