• Adaliana Sorg Mousessian, Clarisse Pereira Nunes da Silva, Sueli Mieko Oba-Shinjo, Angelos G Kolias, Wellingson Silva Paiva, and Nagahashi MarieSuely KazueSKLaboratory of Molecular and Cellular Biology, Department of Neurology, Faculty of Medicina FMUSP, University of São Paulo, Sao Paulo, Brazil..
• Laboratory of Molecular and Cellular Biology, Department of Neurology, Faculty of Medicina FMUSP, University of São Paulo, Sao Paulo, Brazil. Electronic address: adaliana.m@usp.br.
• World Neurosurg. 2021 Mar 1; 147: e16-e24.

ObjectiveTraumatic brain injury (TBI) is a health problem worldwide, and therapeutic strategies to enhance brain tissue repair to lessen neurologic sequels are imperative. We aimed to analyze the impact of the inflammatory process in TBI through CXCR4 and CXCR7 chemokine receptors and their ligands' CXCL11 and CXCL12 expression profile in search for potential new druggable targets.MethodsTwelve pericontusional tissues from severe TBI patients submitted to surgical treatment, and 20 control brain tissues from normal autopsy were analyzed for expression profile by real-time quantitative-polymerase chain reaction. CXCR7 and CXCR4 protein expressions were analyzed by immunohistochemistry. The findings were correlated with the clinical evolution.ResultsIncreased gene expression of both receptors and their ligands was observed in TBI compared with controls, presenting high sensitivity and specificity to differentiate TBI from normal control (area under the curve ranging from 0.85 to 0.98, P < 0.001). In particular, CXCR7 expression highly correlated with CXCR4 and both ligands' expressions in TBI. Higher immunoreactions for CXCR7 and CXCR4 were identified in neurons and endothelial cells of TBI samples compared with controls. The patients presenting upregulated chemokine expression levels showed a trend toward favorable clinical evolution at up to 6 months of follow-up.ConclusionsThe neuroprotective trend of CXCR4, CXCR7, CXCL11, and CXCL12 in TBI observed in this initial analysis warrants further studies with more patients, analyzing the involved signaling pathways for the development of new therapeutic strategies for TBI.Copyright © 2020 Elsevier Inc. All rights reserved.

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