Traumatic brain injury in mice induces changes in the expression of the XCL1/XCR1 and XCL1/ITGA9 axes
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ARTICLE
Traumatic brain injury in mice induces changes in the expression of the XCL1/XCR1 and XCL1/ITGA9 axes Agata Ciechanowska1 · Katarzyna Popiolek‑Barczyk1 · Katarzyna Ciapała1 · Katarzyna Pawlik1 · Marco Oggioni2 · Domenico Mercurio2 · Maria‑Grazia de Simoni2 · Joanna Mika1 Received: 29 July 2020 / Revised: 23 October 2020 / Accepted: 27 October 2020 © The Author(s) 2020
Abstract Background Every year, millions of people suffer from various forms of traumatic brain injury (TBI), and new approaches with therapeutic potential are required. Although chemokines are known to be involved in brain injury, the importance of X-C motif chemokine ligand 1 (XCL1) and its receptors, X-C motif chemokine receptor 1 (XCR1) and alpha-9 integrin (ITGA9), in the progression of TBI remain unknown. Methods Using RT-qPCR/Western blot/ELISA techniques, changes in the mRNA/protein levels of XCL1 and its two receptors, in brain areas at different time points were measured in a mouse model of TBI. Moreover, their cellular origin and possible changes in expression were evaluated in primary glial cell cultures. Results Studies revealed the spatiotemporal upregulation of the mRNA expression of XCL1, XCR1 and ITGA9 in all the examined brain areas (cortex, thalamus, and hippocampus) and at most of the evaluated stages after brain injury (24 h; 4, 7 days; 2, 5 weeks), except for ITGA9 in the thalamus. Moreover, changes in XCL1 protein levels occurred in all the studied brain structures; the strongest upregulation was observed 24 h after trauma. Our in vitro experiments proved that primary murine microglial and astroglial cells expressed XCR1 and ITGA9, however they seemed not to be a main source of XCL1. Conclusions These findings indicate that the XCL1/XCR1 and XCL1/ITGA9 axes may participate in the development of TBI. The XCL1 can be considered as one of the triggers of secondary injury, therefore XCR1 and ITGA9 may be important targets for pharmacological intervention after traumatic brain injury. Graphic abstract
Keywords TBI · Chemokine · XCL1 · XCR1 · ITGA9 · Microglia · Astroglia Extended author information available on the last page of the article
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Introduction Traumatic brain injury (TBI) is a condition that is caused by sudden damage to the central nervous system (CNS) due to accidents, violence, or sport activity and is a major urgent medical need. TBI is extremely difficult to treat, since it leads to secondary injury as a consequence of blood–brain barrier (BBB) disruption, cell death, ischemia, and hemorrhage [1]. Because the commonly used therapies are insufficient and complicated, new approaches that are based on the identification of new, potential therapeutic targets could help us develop more accurate reactions in an effort to address the consequences of TBI. Neuronal damage in brain structures leads to primary cell death, which is induced directly by the trauma, and to the subsequent death of neurons caused by secondary cascades [2]. The complexity of the neuroimmunological responses that
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