title: Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage.
abstract: Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice. Permeability of BBB was measured with Evans Blue assay and brain oedema was detected by measurement of brain water content. Expressions of NF-κB, TLR4, occludin, ZO-1, IL-1β, TNF-α, Bax, and Bcl-2 were determined by Western Blot. Neutrophils, microglia were measured by immunohistochemistry staining, neuronal apoptosis was measured by TUNEL and NeuN co-stained. Administration of MPSS post-ICH significantly reduced permeability of the BBB and brain oedema and upregulated expression of ZO-1 and Occludin. MPSS inhibited inflammatory responses, including reducing proinflammatory cytokines (IL-1β, TNF-α), suppressing infiltration of neutrophils and activation of microglia. This was accompanied by attenuated activation of the TLR4/NF-κB signalling pathway. In addition, MPSS reduced neuronal apoptosis through increasing Bcl-2 expression and reducing Bax expression. MPSS suppressed inflammatory responses, attenuated disruption of the BBB and reduced neuronal apoptosis, contributing to reduction of secondary brain injury after ICH. These results suggest that MPSS may be a potential therapy for ICH.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, People's Republic of China.
authors.forename: WeiWei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, People's Republic of China.
authors.forename: Yingang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, People's Republic of China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China. Electronic address: zhuxingen2008@163.com.
authors.forename: Xingen
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China. Electronic address: doctorzhangyan@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011897:Random Allocation
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018696:Neuroprotective Agents; D008776:Methylprednisolone Hemisuccinate
keywords: Blood-brain barrier; ICH; Inflammation; Methylprednisolone sodium succinate; Mouse model; Oedema