PDF(Pubmed)
Abstract：
OBJECTIVE: Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.
METHODS: We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).
RESULTS: rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.
CONCLUSIONS: Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.
METHODS: We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).
RESULTS: rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.
CONCLUSIONS: Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.
摘要：
目的：由于治疗选择有限，缺血性卒中在医学研究中仍然是一个挑战。重组人组织纤溶酶原激活剂（rtPA）是再通的主要治疗方法。然而,近50％的患者出现并发症，导致无效的再灌注。导致无效再灌注的确切因素仍不清楚；然而，最近的研究表明，免疫细胞，特别是中性粒细胞，可能通过中性粒细胞胞外陷阱的形成等机制影响rtPA溶栓的结果。本研究旨在探讨rtPA对中性粒细胞的非溶栓作用，并强调其对无效再灌注的贡献。
方法：我们评估了rtPA治疗对大鼠大脑中动脉闭塞的影响。我们还评估了大量脑缺血（MCI）患者中rtPA治疗后的中性粒细胞浸润和活化。
结果：rtPA增加了中性粒细胞向脑微血管的浸润，并恶化了缺血期间的血脑屏障损伤。它还增加了MCI患者的中性粒细胞计数。
结论：中性粒细胞在促进缺血性损伤和血脑屏障破坏中起关键作用，使它们成为潜在的治疗目标。
方法：我们评估了rtPA治疗对大鼠大脑中动脉闭塞的影响。我们还评估了大量脑缺血（MCI）患者中rtPA治疗后的中性粒细胞浸润和活化。
结果：rtPA增加了中性粒细胞向脑微血管的浸润，并恶化了缺血期间的血脑屏障损伤。它还增加了MCI患者的中性粒细胞计数。
结论：中性粒细胞在促进缺血性损伤和血脑屏障破坏中起关键作用，使它们成为潜在的治疗目标。
