Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration
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Yip, P., Carrillo-Jimenez, A., King, P., Vilalta, A., Nomura, K., Chau, C., Egerton, A., et al. (2017). Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration. Scientific Reports, 7 (41689)https://doi.org/10.1038/srep41689
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.
We thank Drs B. Joseph, D. Sheer and M. Branco for providing us with reagents. A.C.-J. is supported by a pre-doctoral fellowship from Spanish Ministerio de Educación, Cultura y Deporte. This work has been supported by grants from the Spanish Ministerio SAF2015–64171R (MINECO/FEDER, UE), Blizard Research Theme grants, Blizard Institute, Queen Mary University of London. M.A.B has been funded by the Barts Charity Centre for Trauma Sciences (C4TS) and the Wellcome Trust Institutional Strategic Support Fund (ISSF).
External DOI: https://doi.org/10.1038/srep41689
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263684