Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage.

Autor: Liao J; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China., Duan Y; Department of Radiology, Xiangya Hospital, Central South University, Changsha, China., Liu Y; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China., Chen H; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China., An Z; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China., Chen Y; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China., Su Z; Department of Neurosurgery, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK., Usman AM; Department of Neurosurgery, Allied Hospital Faisalabad, Sargodha Road, Faisalabad 38000, Pakistan., Xiao G; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Diagnosis and Treatment Center for Hydrocephalus, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xiaogelei@csu.edu.cn.
Jazyk: angličtina
Zdroj: Brain research bulletin [Brain Res Bull] 2024 Oct 01; Vol. 216, pp. 111045. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1016/j.brainresbull.2024.111045
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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