Search

Neuroinflammation occurs in the acute phase of spinal cord injury (SCI) and inhibits neural regeneration. In mouse models, etizolam (ETZ) is a strong anxiolytic with unclear effects on SCI. This study investigated the effects of short-term administration of ETZ on neuroinflammation and behavior in mice after SCI. We administrated an ETZ (0.5?mg/kg) daily intraperitoneal injection from the day after SCI for 7 days. Mice were randomly divided into three groups (sham group: only laminectomy, saline group, and ETZ group). Inflammatory cytokine concentrations in the injured spinal cord epicenter were measured using an enzyme-linked immunosorbent assay on day 7 after SCI to evaluate spinal cord inflammation in the acute phase. Behavior analysis was performed the day before surgery and on days 7, 14, 28, and 42 after surgery. The behavioral analysis included anxiety-like behavior using the open field test, locomotor function using the Basso Mouse Scale, and sensory function using the mechanical and heat test. Inflammatory cytokine concentrations were significantly lower in the ETZ group than in the saline group in the acute phase after spinal surgery. After SCI, anxiety-like behaviors and sensory functions were comparable between the ETZ and saline groups. ETZ administration reduced neuroinflammation in the spinal cord and improved locomotor function. Gamma-amino butyric acid type A receptor stimulants may be effective therapeutic agents for patients with SCI.

Abstract Purpose Although the use of intraoperative computed tomography (CT)-based navigation systems is unlikely to cause intraoperative contamination more than the use of intraoperative fluoroscopy, the association between intraoperative CT/navigation and surgical site infections (SSIs) remains unclear. We investigated the incidence of SSIs and the association between intraoperative CT/navigation and SSIs for spinal surgeries. Methods Of the 512 patients who underwent spinal surgery between April 2016 and December 2020, 304 underwent C-arm intraoperative fluoroscopy and/or Medtronic O-arm intraoperative CT/navigation system. We investigated the incidence of SSIs in patients with four techniques; no intraoperative imaging C-arm only, O-arm only, and both O- and C-arm used. Multivariate logistic analyses were conducted using the prevalence of SSIs as the dependent variable. The independent variables were age, sex, and potential confounders including preoperative Japanese Orthopaedic Association (JOA) score, use of instrumentation, C-arm, and/or O-arm. Results The incidence of the SSIs in patients with no imaging, C-arm only, O-arm only, and both modalities used was 1.9%, 7.3%, 4.7%, and 8.3%, respectively. There was no significant difference in the incidence of SSIs between the four techniques. Multivariate logistic analyses showed a significant correlation between the prevalence of SSI and JOA scores (odds ratio, 0.878; 95% CI 0.759–0.990) and use of instrumentation (odds ratio, 6.241; 95% CI 1.113–34.985), but not use of O-arm. Conclusions The incidence of the SSIs in patients with only O-arm used was 4.7%. Preoperative clinical status and use of instrumentation, but not use of the O-arm, were associated with SSIs after spinal surgeries.

A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in CD86+ cells in the injury site with MSC-NHC was mainly attributed to NHC. One and eight weeks after injury, we found a greater CD206+/CD86+ cell ratio with MSC-NHC or NHC, but not MSC-PBS, indicating a shift from a pro-inflammatory towards an anti-inflammatory milieu in the injury site. Eight weeks after injury, the injury size was significantly reduced with MSC-NHC, NHC, and MSC-PBS. At this time, astrocyte, and axon presence in the injury site was greater with MSC-NHC compared with MSC-PBS. We did not find a significant effect of NHC on MSC transplant survival, and hind limb function was similar across all groups. However, we did find fewer macrophages at 1 week post-injury, more macrophages polarized towards a pro-regenerative phenotype at 1 and 8 weeks after injury, and reduced injury volume, more astrocytes, and more axons at 8 weeks after injury in rats with MSC-NHC and NHC alone compared with MSC-PBS; these findings were especially significant between rats with MSC-NHC and MSC-PBS. The data support further study in the use of an NHC-MSC combination transplant in the contused spinal cord.

Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent stem cells that can be isolated based on stage-specific embryonic antigen-3 (SSEA-3), a pluripotent stem cell-surface marker. However, their capacities for survival, neurotrophic factor secretion, and neuronal and glial differentiation are unclear in rodents. Here we analyzed mouse adipose tissue-derived Muse cells in vitro. We collected mesenchymal stem cells (MSCs) from C57BL/6 J mouse adipose tissue and separated SSEA-3 + , namely Muse cells, and SSEA-3 – , non-Muse cells, to assess self-renewability; pluripotency marker expression (Nanog, Oct3/4, Sox2, and SSEA-3); spontaneous differentiation into endodermal, mesodermal, and ectodermal lineages; and neural differentiation capabilities under cytokine induction. Neurally differentiated Muse and non-Muse cell functions were assessed by calcium imaging. Antioxidant ability was measured to assess survival under oxidative stress. Brain-derived neurotrophic factor (BDNF), vascular endothelial cell growth factor (VEGF), and hepatocyte growth factor (HGF) secretion were analyzed in enzyme-linked immunosorbent assays. SSEA-3 + Muse cells (6.3 ± 1.9% of mouse adipose-MSCs), but not non-Muse cells, exhibited self-renewability, spontaneous differentiation into the three germ layers, and differentiation into cells positive for Tuj-1 (27 ± 0.9%), O4 (17 ± 3.4%), or GFAP (23 ± 1.3%) under cytokine induction. Neurally differentiated Muse cells responded to KCl depolarization with greater increases in cytoplasmic Ca 2+ levels than non-Muse cells. Cell survival under oxidative stress was significantly higher in Muse cells (50 ± 2.7%) versus non-Muse cells (22 ± 2.8%). Muse cells secreted significantly more BDNF, VEGF, and HGF (273 ± 12, 1479 ± 7.5, and 6591 ± 1216 pg/mL, respectively) than non-Muse cells (133 ± 4.0, 1165 ± 20, and 2383 ± 540 pg/mL, respectively). Mouse Muse cells were isolated and characterized for the first time. Muse cells showed greater pluripotency-like characteristics, survival, neurotrophic factor secretion, and neuronal and glial-differentiation capacities than non-Muse cells, indicating that they may have better neural-regeneration potential.