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- β1, TGF- β2) 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.

Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

“…Interestingly, the role of CAT in antiapoptosis has also been reported with neuroprotective effects against acute focal ischemic stroke (Wang et al, 2020). Because the death of neurons during SCI is the main reason for damaged motor function, we speculate that the neuroprotective effects of CAT can alleviate the neuronal death caused by SCI (Heller et al, 2021).…”

Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual‐Signal Transform‐Based Selenium Antioxidant

“…As reported previously, the intracellular antioxidant machinery consists of various enzymatic and non-enzymatic antioxidants, such as GSH and Se, which reduce oxidative stress via scavenging ROS or free radicals. [32,33] Hence, the antioxidant ability of Se NPs in a neuronal injury model was examined, in which the injured neurons were treated with various concentrations of biosafe Se NPs and the repair effect of Se NPs on injured neurons was monitored. As shown in Figure 2c, the fluorescence intensity of the microtubule dye for tubulin increased when the injured neurons were treated with Se NPs.…”

Infiltrating circulating monocytes provide an important source of BMP4 at the early stage of spinal cord injury

“…Once the injury has manifested clinically, conventional treatment measures, including early surgical decompression and high-dose corticosteroid therapy, only provide limited therapeutic effect ( Karsy and Hawryluk, 2019 ). One prominent pathological feature of SCI is breakdown of the blood–spinal cord barrier (BSCB), which alters the composition of the microenvironment of the central nervous system (CNS) by allowing the invasion of circulating signals, especially monocytes, into the injured spinal cord ( Diaz et al, 2021 ; Gao et al, 2021 ; Döring et al, 2015 ; Heller et al, 2021 ). A growing body of evidence ( Döring et al, 2015 ; Heller et al, 2021 ; Durafourt et al, 2012 ; Girard et al, 2013 ; Yamasaki et al, 2014 ) has demonstrated that infiltrating monocyte-derived macrophages (MDMs) play a critical role in the regulation of inflammation and nerve regeneration, which might significantly influence neurological recovery.…”

“…One prominent pathological feature of SCI is breakdown of the blood–spinal cord barrier (BSCB), which alters the composition of the microenvironment of the central nervous system (CNS) by allowing the invasion of circulating signals, especially monocytes, into the injured spinal cord ( Diaz et al, 2021 ; Gao et al, 2021 ; Döring et al, 2015 ; Heller et al, 2021 ). A growing body of evidence ( Döring et al, 2015 ; Heller et al, 2021 ; Durafourt et al, 2012 ; Girard et al, 2013 ; Yamasaki et al, 2014 ) has demonstrated that infiltrating monocyte-derived macrophages (MDMs) play a critical role in the regulation of inflammation and nerve regeneration, which might significantly influence neurological recovery. Thus, therapeutic strategies targeting the invasion of circulating monocytes should be addressed for the treatment of SCI.…”