Pastorello Ylenia, Russo Aurelio Pio, Bănescu Claudia, Caprio Vittorio, Gáll Zsolt, Potempa Lawrence, Cordoș Bogdan, Di Napoli Mario, Slevin Mark
Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, ROU.
Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, ROU.
Cureus. 2024 May 20;16(5):e60682. doi: 10.7759/cureus.60682. eCollection 2024 May.
Introduction The neurovascular unit (NVU), comprising vascular and glial cells along with neurons, is vital for maintaining the blood-brain barrier (BBB) and cerebral homeostasis. Dysfunction of the NVU is implicated in key neurodegenerative disorders such as Alzheimer's disease (AD). Monomeric C-reactive protein (mCRP), the dissociated form of native, pentameric C-reactive protein (pCRP), is associated with enhanced pro-inflammatory responses in the vascular system, leading to increased permeability and potential NVU disruption. Methods This study utilized ApoE-/- mice receiving a high-fat diet which were injected intraperitoneally with either mCRP or mCRP together with a small molecule inhibitor (C10M) and investigated the deposition of mCRP and CD105 expression in the brain parenchyma and its localization within the microvasculature. Results Histological analysis revealed significant mCRP deposition in brain microvessels and neurons, indicating potential disruption of the BBB and neuronal damage. Moreover, co-administration of C10M effectively blocked mCRP accumulation in the brain parenchyma, suggesting its potential as a therapeutic agent for effectively inhibiting inflammation-associated degenerative changes. Immunohistochemical staining demonstrated co-localization of mCRP with CD105, indicating potential angiogenic activation and increased susceptibility to inflammatory insult. Discussion These findings provide evidence supporting the potential role of mCRP as a contributor to neuroinflammation in individuals with chronic systemic inflammation. Conclusion Further studies in human subjects should help validate the efficacy of C10M in preventing or halting neurodegeneration in conditions such as AD and stroke-associated dementia.
引言 神经血管单元（NVU）由血管细胞、神经胶质细胞和神经元组成，对于维持血脑屏障（BBB）和脑内环境稳定至关重要。NVU功能障碍与阿尔茨海默病（AD）等关键神经退行性疾病有关。单体C反应蛋白（mCRP）是天然五聚体C反应蛋白（pCRP）的解离形式，与血管系统中促炎反应增强有关，导致通透性增加和潜在的NVU破坏。方法 本研究利用接受高脂饮食的载脂蛋白E基因敲除（ApoE-/-）小鼠，腹腔注射mCRP或mCRP与小分子抑制剂（C10M），研究mCRP在脑实质中的沉积以及CD105表达及其在微血管中的定位。结果 组织学分析显示脑微血管和神经元中有显著的mCRP沉积，表明血脑屏障可能遭到破坏以及神经元损伤。此外，联合给予C10M可有效阻断mCRP在脑实质中的蓄积，表明其作为有效抑制炎症相关退行性变化的治疗剂的潜力。免疫组织化学染色显示mCRP与CD105共定位，表明可能存在血管生成激活以及对炎症损伤的易感性增加。讨论 这些发现提供了证据，支持mCRP在慢性全身性炎症个体的神经炎症中起作用的潜在作用。结论 在人类受试者中进行的进一步研究应有助于验证C10M在预防或阻止AD和中风相关性痴呆等疾病中的神经退行性变方面的疗效。
