Evaluation of СХС chemokine levels in cerebrospinal fluid of patients with brain contusions

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Abstract

Traumatic brain injury (TBI) is among the most common forms of neurological pathology. In traumatic brain injury, axonal damage occurs not only as a result of direct cytotoxic interactions, but also due to activation of pro-inflammatory cytokines and chemokines, which play a crucial role in development and maintenance of neuroinflammation. At the early terms after brain trauma, there occurs both activation of microglia, and formation of a pool of T cell subsets able to produce various chemokines. The aim of this study was to assess the contents of chemokines (CXCL8/MIG, CXCL9/IP-10, CXCL10/I-TAC) in cerebrospinal fluid (CSF) of patients with brain contusion of varying severity within the first 24 hours after hospital admission. The study included 86 patients diagnosed with “TBI: brain contusion,” who were divided into three groups based on the injury severity. A comparison group consisted of patients with brain concussion (n = 24). Obtaining CSF from healthy individuals is challenging due to absence of clinical indications for lumbar puncture. Chemokine concentrations (pg/mL) were measured by means of multiplex analysis based on xMAP technology (Luminex, USA), using Milliplex MAP test systems (Millipore, USA). The results showed a trend toward increased chemokine levels correlating with more pronounces severity of brain injury. Notably, CXCL9/MIG levels were elevated in all patients with brain injury (p < 0.05), unlike CXCL8/IL-8, which showed significant increases only in the 4th group (severe TBI), and CXCL10/IP-10, which was significantly elevated in both the 3rd (moderate TBI) and 4th groups. Specifically, in the 4th group (severe TBI), levels of CXCL8/IL-8 were increased 3.5 times, CXCL9/MIG showed a 9-fold increase, and CXCL10/IP-10 was 3 times higher than in control group (1st group, mild TBI). To evaluate the diagnostic value of these changes, ROC analysis was performed, establishing a clinically significant chemokine thresholds that serve as highly informative markers of neural tissue damage. In conclusion, assessment of CXCL8, CXCL9, and CXCL10 levels in CSF following brain contusion provides valuable insights into their role in disease progression, i.e., recruiting T helper cells and neutrophils from peripheral blood into neural tissue and sustaining neuroinflammatory processes.

About the authors

Anna O. Norka

Saint Petersburg Pasteur Institute; First St. Petersburg Pavlov State Medical University

Author for correspondence.
Email: norka-anna@mail.ru

PhD (Medicine), Assistant Professor, Department of Immunology, First St. Petersburg Pavlov State Medical University; Neurologist, Medical Centre, Saint Petersburg Pasteur Institute

Russian Federation, St. Petersburg; St. Petersburg

S. V. Vorobyev

Almazov National Medical Research Centre; St. Petersburg State Pediatric Medical University

Email: norka-anna@mail.ru

PhD, MD (Medicine), Associate Professor, Chief Researcher, Research Laboratory of Neurology and Neurorehabilitation, Almazov National Medical Research Centre; Professor, Department of Clinical Laboratory Diagnostics, St. Petersburg State Pediatric Medical University

Russian Federation, St. Petersburg; St. Petersburg

R. N. Kuznetsova

Saint Petersburg Pasteur Institute; First St. Petersburg Pavlov State Medical University

Email: norka-anna@mail.ru

PhD (Medicine), Associate Professor, Department of Immunology, First St. Petersburg Pavlov State Medical University; Allergist-Immunologist, Medical Centre, Saint Petersburg Pasteur Institute

Russian Federation, St. Petersburg; St. Petersburg

Z. R. Korobova

Saint Petersburg Pasteur Institute; First St. Petersburg Pavlov State Medical University

Email: norka-anna@mail.ru

Junior Researcher, Laboratory of Molecular Immunology, Saint Petersburg Pasteur Institute; Senior Assistant, Department of Immunology, First St. Petersburg Pavlov State Medical University

Russian Federation, St. Petersburg; St. Petersburg

Areg A. Totolian

Saint Petersburg Pasteur Institute; First St. Petersburg Pavlov State Medical University

Email: norka-anna@mail.ru

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Science, Head, Laboratory of Molecular Immunology, Director, Saint Petersburg Pasteur Institute; Head, Department of Immunology, First St. Petersburg Pavlov State Medical University

Russian Federation, St. Petersburg; St. Petersburg

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Supplementary files

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2. Figure 1. ROC curves and AUC of CXCL9/MIG (pg/mL) in the cerebrospinal fluid

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3. Figure 2. ROC curves and AUC of CXCL10/IP-10 (pg/mL) in the cerebrospinal fluid

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4. Figure 3. ROC curve and AUC of CXCL8/IL-8 (pg/mL) in patients with severe head injury in the cerebrospinal fluid

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Copyright (c) 2025 Norka A.O., Vorobyev S.V., Kuznetsova R.N., Korobova Z.R., Totolian A.A.

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