Exploring macrophage differentiation and its relation to Modic changes in human herniated disc tissue.

Introduction: Cervical- and lumbosacral radiculopathy symptoms due to disc herniation are likely to be influenced by macrophage infiltration of the herniated disc. Vertebral endplate changes are hypothesized to, at least partially, correlate to the inflammatory condition of the disc and its environment. Research question: The present study aims to evaluate several immunohistochemical M1-and M2-markers for their suitability to discern pro-inflammatory M1-and anti-inflammatory M2 macrophage differentiation patterns in herniated intervertebral disc tissue. In addition, their associations with Modic changes (MC) of the vertebral endplates will be evaluated. Materials and methods: Herniated disc samples were collected from 45 patients undergoing surgery for cervical- or lumbosacral radiculopathy. Samples were processed for immunohistochemistry and stained for the presence of macrophages: CD68 (macrophage marker), CD40 (M1), iNOS (M1), CD192 (M1), CD163 (M2), Arg1 (M2) and CD209 (M2). T-cells (CD3) and neutrophil (CD15) expressions were studied additionally. Results: CD68 positive cells were present with a median density of 50/cm2, M2 markers CD163 and CD209 were expressed most dominantly, followed by M1 marker CD192. Other M1/M2 markers, T-cell and neutrophil expression was limited. Lumbar samples showed higher expression of iNOS and Arg1 compared to cervical samples. Presence of Modic changes was associated with higher levels of CD68+ cells (p â€‹= â€‹0.046), but no significant differences in M1/M2 markers were found. Discussion and conclusion: For studying M1 macrophages, CD192 is the most suitable marker due to its high expression; whereas for M2 macrophages, this is CD163 due to its high expression and selectivity. Further, the relatively high expression of M2 markers indicates predominance of anti-inflammatory over pro-inflammatory macrophages in symptomatic lumbar and cervical disc herniations. No associations between M1/M2 markers and MC were seen in this limited number of samples. In order to further explore the role of macrophage differentiation and its relation with MC in radiculopathy, a large prospective trial with elaborate clinical follow-up is required.

Lumbar disc extrusions reduce faster than bulging discs due to an active role of macrophages in sciatica.

OBJECTIVE: This retrospective observational histological study aims to associate the size and type of disc herniation with the degree of macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. METHODS: Disc tissue of 119 sciatica patients was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10/cm2), moderate (10-100/cm2), and considerable (> 100/cm2) macrophage infiltration. All 119 patients received an MRI at baseline, and 108 received a follow-up MRI at 1-year. MRIs were reviewed for the size and type of the disc herniations, and for Modic changes in the vertebral endplates. RESULTS: Baseline characteristics and duration of symptoms before surgery were comparable in all macrophage infiltration groups. The degree of macrophage infiltration was not associated with herniation size at baseline, but significantly associated with reduction of size of the herniated disc at 1-year post surgery. Moreover, the degree of macrophage infiltration was higher in extrusion in comparison with bulging (protrusion) of the disc. Results were comparable in patients with and without Modic changes. CONCLUSION: Macrophage infiltration was positively associated with an extruded type of disc herniation as well as the extent of reduction of the herniated disc during 1-year follow-up in patients with sciatica. This is an indication that the macrophages play an active role in reducing herniated discs. An extruded disc herniation has a larger surface for the macrophages to adhere to, which leads to more size reduction.

The contradictory effect of macrophage-related cytokine expression in lumbar disc herniations: a systematic review.

PURPOSE: Sciatic symptoms due to lumbar disc herniation are likely to be caused not solely by mechanical compression of the nerve root, but also by pain-inducing elements from inflammatory processes. Key components in the inflammatory reaction are M1 and M2 macrophages, with the M1 type being associated with pro-inflammatory processes and M2 with anti-inflammatory-processes. METHOD: The present systematic review summarizes all studies on associations between M1 and M2 macrophages and their related inflammation factors and pain symptoms in lumbar disc herniations. Literature search was performed using an optimally sensitive search string. Studies were selected for inclusion by means of predefined inclusion and exclusion criteria and subsequently graded for risk of bias. A total of 14 studies were included. Overall risk of bias was moderate (8/14), and three studies had high risk of bias and three has low risk of bias. RESULTS: Regarding M1-related cytokines, high levels of TNF-α, TNFR1, IL-6, IL-8, and IFN-γ were all associated high VAS scores. In contrast, high levels of TNFR2 were associated with lower VAS scores. Moreover, no associations were found for IL-1a and IL-1ß. Results regarding M2-related cytokines revealed the opposite: high levels of both IL-4 and IL-10 were associated with lower VAS scores. No associations were established for TGF-ß. Moreover, the presence of macrophages (CD68) was negatively associated with VAS scores. CONCLUSION: While M1-related pro-inflammatory cytokines worsen pain symptoms, M2-related anti-inflammatory cytokines alleviate pain symptoms. Nevertheless, the present evidence is limited, and further research on the underlying pathophysiological mechanism in sciatica is required. These slides can be retrieved under Electronic Supplementary Material.

Rate constants and branching ratios for the dissociative recombination of C3D(+)7 and C4D(+)9.

Product branching ratios and thermal rate coefficients for the dissociative recombination of C3D(+)7 and C4D(+)9 have been measured in the ion storage ring CRYRING. The results for C3D(+)7 are believed to be slightly more accurate than those obtained earlier for C3H(+)7. Only the C-C bond breaking channels could be measured for C4D(+)9 and were found to be in excellent agreement with earlier data.

An enhanced cosmic-ray flux towards zeta Persei inferred from a laboratory study of the H3+-e- recombination rate.

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many molecules. In dense interstellar clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density and temperature. But observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. Models of diffuse clouds have, however, been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons (e-), the electron fraction, and the cosmic-ray ionization rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards Persei) where the electron fraction is already known. From these, we find that the cosmic-ray ionization rate along this line of sight is 40 times faster than previously assumed. If such a high cosmic-ray flux is ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.