Abstract:
Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution in the acute phase of ICH, though the precise mechanisms remain unclear. Recent findings have highlighted the glymphatic system (GS) as a crucial component in intracranial cerebrospinal fluid circulation, playing a significant role in hematoma clearance post-ICH. This study investigates the link between SIM efficacy in hematoma resolution and the GS. Our experimental results show that SIM alleviates GS damage in ICH-induced rats, resulting in improved outcomes such as reduced brain edema, neuronal apoptosis, and degeneration. Further analysis reveals that SIM\'s effects are mediated through the VEGF-C/VEGFR3/PI3K-Akt pathway. This study advances our understanding of SIM\'s mechanism in promoting intracranial hematoma clearance and underscores the potential of targeting the GS for ICH treatment.
摘要:
目前的临床实践主要依靠手术干预来清除脑出血(ICH)患者的血肿,由于缺乏有效的药物治疗。先前的研究表明,辛伐他汀(SIM)可以增强脑出血急性期的血肿吸收和消退,尽管确切的机制尚不清楚。最近的发现强调了淋巴系统(GS)是颅内脑脊液循环的重要组成部分,在ICH后血肿清除中起重要作用。这项研究调查了SIM在血肿分辨率中的疗效与GS之间的联系。我们的实验结果表明,SIM减轻了ICH诱导的大鼠的GS损伤,导致改善的结果,如减少脑水肿,神经元凋亡,和退化。进一步的分析表明,SIM的作用是通过VEGF-C/VEGFR3/PI3K-Akt途径介导的。这项研究提高了我们对SIM促进颅内血肿清除的机制的理解,并强调了靶向GS治疗ICH的潜力。