title: Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration.
abstract: Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury. We report that galectin-3 can bind to TLR-4, and that administration of a neutralizing antibody against galectin-3 decreases the expression of IL-1β, IL-6, TNFα and NOS2 and promotes neuroprotection in the cortical and hippocampal cell populations after head injury. Long-term analysis demonstrated a significant neuroprotection in the cortical region in the galectin-3 knockout animals in response to TBI. These results suggest that following head trauma, released galectin-3 may act as an alarmin, binding, among other proteins, to TLR-4 and promoting inflammation and neuronal loss. Taking all together, galectin-3 emerges as a clinically relevant target for TBI therapy.
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Ping Kei
authors.initials: PK
authors.lastname: Yip
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Sevilla, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Carrillo-Jimenez
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: King
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilalta
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Koji
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Chi Cheng
authors.initials: CC
authors.lastname: Chau
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Alexander Michael Scott
authors.initials: AM
authors.lastname: Egerton
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.|Chang Gung Medical College and University, Chang Gung Memorial Hospital, Department of Neurosurgery, 5 Fu-Shin Street, Linkou, Taiwan.
authors.forename: Zhuo-Hao
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Ashray Jayaram
authors.initials: AJ
authors.lastname: Shetty
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Jordi L
authors.initials: JL
authors.lastname: Tremoleda
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Meirion
authors.initials: M
authors.lastname: Davies
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, BMC B11, 221 84 Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Deierborg
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom.
authors.forename: Guy Charles
authors.initials: GC
authors.lastname: Brown
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Adina Teodora
authors.initials: AT
authors.lastname: Michael-Titus
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Sevilla, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Venero
authors.affiliation: Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Burguillos
mesh_terms: D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007109:Immunity; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D037502:Galectin 3