TY - JOUR
T1 - Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration
AU - Yip, Ping Kei
AU - Carrillo-Jimenez, Alejandro
AU - King, Paul
AU - Vilalta, Anna
AU - Nomura, Koji
AU - Chau, Chi Cheng
AU - Egerton, Alexander Michael Scott
AU - Liu, Zhuo Hao
AU - Shetty, Ashray Jayaram
AU - Tremoleda, Jordi L.
AU - Davies, Meirion
AU - Deierborg, Tomas
AU - Priestley, John V.
AU - Brown, Guy Charles
AU - Michael-Titus, Adina Teodora
AU - Venero, Jose Luis
AU - Burguillos, Miguel Angel
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/1/27
Y1 - 2017/1/27
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85010987773
U2 - 10.1038/srep41689
DO - 10.1038/srep41689
M3 - 文章
C2 - 28128358
AN - SCOPUS:85010987773
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
M1 - 41689
ER -