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Predicting neurological recovery after traumatic spinal cord injury by time-resolved analysis of monocyte subsets.

Abstract

Monocytes and lymphocytes elicit crucial activities for the regenerative processes after various types of injury. The survival of neurons exposed to mechanical and oxidative stress after traumatic spinal cord injury (TSCI) depends on a multitude of factors. The current study sought to evaluate a correlation between remission after TSCI and dynamics of monocyte subsets in respect to the lymphocytes' responsive potential, cytokine expression, patterns of trace element concentration and clinical covariates. We examined prospectively 18 (3 female, 15 male) patients after TSCI. Blood samples were drawn at admission and 4 h, 9 h, 12 h, 1 and 3 days as well as 1 and 2 weeks and 1, 2 and 3 months after the trauma. Analysis of cytokines (CCL-2, IL-10, Enolase 2, CXCL-12, TGF- beta1, TGF- beta2) was performed using a multiplex cytokine panel. Plasma trace element concentrations of selenium, copper and zinc were determined by total reflection X-ray fluorescence analysis, Neopterin, selenoprotein P (SELENOP) and ceruloplasmin (CP) by enzyme-linked immunosorbent assay (ELISA) and selenium binding protein 1 (SELENBP1) by luminometric immunoassay (LIA). The responsive potential of lymphocytes was assessed via transformation tests. The monocyte subsets (classical, intermediate, and non-classical) and expression of CD14, CD16, CXCR4 and intracellular IL-10 were identified using a multi-colour flow cytometry analysis. The dynamics of the cluster of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes differed significantly between patients with an absence of neurological remission (G0) from those with an improvement (G1) by 1 or 2 AIS steps (Kruskal-Wallis Test, p = 0.010, G0 < G1, AIS+: 1 < G1, AIS+: 2) in the first 24 h. These dynamics were associated inversely with an increase in Enolase and SELENBP1 14 d after the injury. In the elastic net regularised model, we identified an association between the increase of a subpopulation of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes and exacerbated immune response within 24 h after the injury. These findings are reflected in the consistently elevated response to mitogen stimulation of the lymphocytes of patients with significant neurological remission. Early elevated concentrations of CD14-/CD16+/IL10+/CXCR4int monocytes were related to higher odds of CNS regeneration and enhanced neurological remission. The cluster-dynamics of CD14-/CD16+/IL10+/CXCR4int monocytes in the early-acute phase after the injury revealed a maximum of prognostic information regarding neurological remission (mean parameter estimate: 0.207; selection count: 818/1000 repetitions). We conclude that early dynamics in monocyte subsets allow a good prediction of recovery from TSCI.

Authors: Heller RA, Seelig J, Crowell HL, Pilz M, Haubruck P, Sun Q, Schomburg L, Daniel V, Moghaddam A, Biglari B,
Journal: Brain; 2021 Nov 29;144(10):3159-3174. . doi:10.1093/brain/awab203
Year: 2021
PubMed: PMID: 34022039 (Go to PubMed)