title: Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice.
abstract: BACKGROUND
  Macrophages are involved in demyelination in many brain diseases. However, the role of macrophages in the recovery phase of the ischemic brain is unknown. The present study aims to explore the role of macrophages in the ischemic brain injury and tissue repair following a 90-min transient middle cerebral artery occlusion in mice.
  
  
  METHODS
  Clodronate liposomes were injected into mice to deplete periphery macrophages. These mice subsequently underwent middle cerebral artery occlusion. F4/80(+) and CD68(+) cells were examined in the mouse spleen and brain to confirm macrophage depletion at 14 days after middle cerebral artery occlusion. Modified neurological severity scores were used to evaluate the behavioral function between 1 and 14 days after middle cerebral artery occlusion. MBP, Iba1, and CD31 immunostaining were performed to determine myelin lesion, microglia activation, and microvessel density.
  
  
  RESULTS
  Clodronate liposomes depleted 80 % of the macrophages in the mouse spleen and reduced macrophage infiltration in the mouse brain. Macrophage depletion reduced the myelin damage in the ipsilateral striatum and microglia activation in both the ipsilateral cortex and striatum, enhanced the microvessel density in the peri-infarct region, attenuated brain atrophy, and promoted neurological recovery following middle cerebral artery occlusion.
  
  
  CONCLUSIONS
  Our results suggested that macrophage depletion is a potential intervention that can promote tissue repair and remodeling after brain ischemia, reduce demyelination and microglia activation, and enhance focal microvessel density.
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. mayuanyuan555@163.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200030, China. liyaning_2008@126.com.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200030, China. mantou863782935@126.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. 1258499596@qq.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. 260446839@qq.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200030, China. ytwang@sjtu.edu.cn.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200030, China. zhangzhij@gmail.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China. gyyang0626@163.com.|Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, Shanghai, 200030, China. gyyang0626@163.com.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology* / Q000628:therapy*; D002135:Calcium-Binding Proteins; D004002:Clodronic Acid / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D013997:Time Factors
chemical_list: C100745:Aif1 protein, rat; D015703:Antigens, CD; D050071:Bone Density Conservation Agents; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D004002:Clodronic Acid