Galectin-3 released in response to traumatic brain injury acts as an alarmin orchestrating brain immune response and promoting neurodegeneration

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.

Carrillo-Jimenez, AlejandroUniversity of Seville,University Hospital Virgen del Rocío (author)
King, PaulQueen Mary University (author)
Vilalta, AnnaUniversity of Cambridge (author)
Nomura, KojiUniversity of Cambridge (author)
Chau, Chi ChengQueen Mary University (author)
Egerton, Alexander Michael ScottQueen Mary University (author)
Liu, Zhuo HaoQueen Mary University,Chang Gung University (author)
Shetty, Ashray JayaramQueen Mary University (author)
Tremoleda, Jordi L.Queen Mary University (author)
Davies, MeirionQueen Mary University (author)
Deierborg, TomasLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)expb-tol (author)
Priestley, John V.Queen Mary University (author)
Brown, Guy CharlesUniversity of Cambridge (author)
Michael-Titus, Adina TeodoraQueen Mary University (author)
Venero, Jose LuisUniversity of Seville,University Hospital Virgen del Rocío (author)
Burguillos, Miguel AngelQueen Mary University (author)
Queen Mary UniversityUniversity of Seville (creator_code:org_t)

By the author/editor: Yip, Ping Kei; Carrillo-Jimenez ...; King, Paul; Vilalta, Anna; Nomura, Koji; Chau, Chi Cheng; show more...; Egerton, Alexand ...; Liu, Zhuo Hao; Shetty, Ashray J ...; Tremoleda, Jordi ...; Davies, Meirion; Deierborg, Tomas; Priestley, John ...; Brown, Guy Charl ...; Michael-Titus, A ...; Venero, Jose Lui ...; Burguillos, Migu ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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