title: Simvastatin Promotes Hematoma Absorption and Reduces Hydrocephalus Following Intraventricular Hemorrhage in Part by Upregulating CD36.
abstract: We previously found that hematoma worsens hydrocephalus after intraventricular hemorrhage (IVH) via increasing iron deposition and aggravating ependymal cilia injury; therefore, promoting hematoma absorption may be a promising strategy for IVH. Recently, some investigations imply that simvastatin has the ability of accelerating hematoma absorption. Thus, this study was designed to examine the efficacy of simvastatin for IVH in rats. Intracerebral hemorrhage with ventricular extension was induced in adult male Sprague-Dawley rats after autologous blood injection. Simvastatin or vehicle was administered orally at 1 day after IVH and then daily for 1 week. MRI studies were performed to measure the volumes of intracranial hematoma and lateral ventricle at days 1, 3, 7, 14, and 28 after IVH. Motor and neurocognitive functions were assessed at days 1 to 7 and 23 to 28, respectively. Iron deposition, iron-related protein expression, ependymal damage, and histology were detected at day 28. Expression of CD36 scavenger receptor (facilitating phagocytosis) was examined at day 3 after IVH using western blotting and immunofluorescence. Simvastatin significantly increased hematoma absorption ratio, reduced ventricular volume, and attenuated neurological dysfunction post-IVH. In addition, less iron accumulation and more cilia survival was observed in the simvastatin group when compared with the control. What's more, higher expression of CD36 was detected around the hematoma after simvastatin administration. Simvastatin significantly enhanced brain hematoma absorption, alleviated hydrocephalus, and improved neurological recovery after experimental IVH, which may in part by upregulating CD36 expression. Our data suggest that early simvastatin use may be a novel therapy for IVH patients.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Nutrition, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nutrition, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China. fenghua8888@vip.163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, China. zhichen@tmmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D039481:CD11b Antigen / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002452:Cell Count; D002543:Cerebral Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004805:Ependyma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005293:Ferritins / Q000378:metabolism / Q000648:ultrastructure; D005500:Follow-Up Studies; D006406:Hematoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D006849:Hydrocephalus / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D020547:Lateral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D009460:Neurologic Examination; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D039481:CD11b Antigen; D018955:CD36 Antigens; D000960:Hypolipidemic Agents; D005293:Ferritins; D019821:Simvastatin
keywords: Hematoma clearance; Hydrocephalus; Intraventricular hemorrhage; Simvastatin