Microglia and macrophages (MG/MΦ) have a diverse range of functions depending on unique cytokine stimuli, and contribute to neural cell death, repair, and remodeling during central nervous system diseases. While IL-1 has been shown to exacerbate inflammation, it has also been recognized to enhance neuroregeneration. We determined the activating phenotype of MG/MΦ and the impact of IL-1 in an in vivo spinal cord injury (SCI) model of IL-1 knock-out (KO) mice. Moreover, we demonstrated the contribution of IL-1 to both the classical and alternative activation of MG in vitro using an adult MG primary culture.

Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, and other neuronal disorders. Recently, we found that expression of the gene for mouse PACAP (Adcyap1) was greater in animals receiving hMSCs with neural injury such as ischemia. However, the association of PACAP with hMSCs to protect nerve cells against neural injuries is still unclear. Wild-type and PACAP-gene-deficient (Adcyap1 +/− ) mice were subjected to spinal cord transection, and hMSCs (5 × 105 cells) were injected into the intervertebral spinal cord on day 1 post-operation (p.o.). Locomotor activity, injury volume, retention of hMSCs, mouse and human cytokine genes (which contribute to macrophage (MΦ) and microglial activation), and Adcyap1 were evaluated. hMSCs injected into wild-type mice improved locomotor activity and injury volume compared with vehicle-treated mice. In contrast, non-viable hMSCs injected into wild-type mice, and viable hMSCs injected into Adcyap1 +/− mice, did not. Wild-type mice injected with hMSCs exhibited increased Adcyap1 expression, and observed PACAP immunoreaction in neuron-like cells. Gene expression levels for IL-1, tumor necrosis factor α (TNFα), interleukin-10 (IL-10), and transforming growth factor β (TGFβ) decreased, while that for interleukin-4 (IL-4) increased, in hMSC-injected wild-type mice. In contrast, IL-1, TGFβ, and IL-4 gene expression levels were all abolished in hMSC-injected Adcyap1 +/− mice on day 7 post-operation. Moreover, the mice-implanted hMSCs increased an alternative activating macrophage/microglial marker, arginase activity. The human gene profile indicated that hMSCs upregulated the gene of IL-4 and growth factors which were reported to enhance Adcyap1 expression. Finally, we demonstrated that hMSCs express human ADCYAP1 and its receptor gene after the inflammation-related interferon-γ (IFNγ) in vitro. These results suggest that hMSCs attenuate the deleterious effects of SCI by reducing associated inflammatory responses and enhancing IL-4 production. This effect could be mediated in part by cell-cell cross-talk involving the neuropeptide PACAP.

Elongation, defined as the 3-dimensional distance between ligament attachment sites, is a useful metric for evaluating ligament function. However, intraoperative assessment of elongation patterns in osteoarthritic (OA) knees during total knee arthroplasty (TKA) remains limited. To analyze the intraoperative elongation patterns of the medial and lateral collateral ligaments (MCL and LCL) in OA knees using augmented reality (AR) navigation, according to the Coronal Plane Alignment of the Knee classification. A total of 100 OA knees undergoing TKA with AR-based navigation were evaluated. Real-time 3-dimensional elongation of the MCL and LCL was recorded throughout the full range of motion. A ≥10% change in ligament length was defined as significant. Elongation patterns were analyzed by Coronal Plane Alignment of the Knee type. The MCL remained relatively constant during knee flexion, whereas the LCL shortened. Normal elongation patterns (stable MCL with LCL shortening) were observed in 83.3% of type I, 79.2% of type II, 75.0% of type III, and 100% of type IV and V knees. However, atypical patterns were also noted in some type I and II knees. Most OA knees demonstrated ligament elongation patterns similar to those of healthy knees. AR navigation enabled real-time, quantitative 3-dimensional assessment of ligament dynamics and may support individualized intraoperative soft tissue evaluation during TKA.

Background Oxidized regenerated cellulose (ORC) is a biodegradable hemostatic agent widely used in surgical practice. However, its efficacy and safety in total knee arthroplasty (TKA), particularly in simultaneous bilateral procedures, remain underreported. Methods This retrospective study included patients who underwent simultaneous bilateral TKA at our institution. A total of 49 patients were analyzed and divided into two groups: the ORC group (n=21), in which ORC was used intraoperatively, and the non-ORC group (n=28). Perioperative hemoglobin (Hb) and hematocrit (Ht) levels were compared between groups, along with estimated blood loss (EBL) on postoperative days 4 and 7, calculated using the Gross formula. Transfusion rates and postoperative complications were also evaluated. Statistical analyses were performed using the Wilcoxon rank-sum test and chi-squared test. Results No significant preoperative differences in Hb or Ht values were observed between groups. However, both postoperative Hb/Ht levels and EBL on postoperative days 4 and 7 were significantly lower in the ORC group (p<0.05). No significant difference in transfusion rate was found between groups. Importantly, no postoperative complications directly related to ORC use were identified. Conclusion ORC demonstrated effective and safe hemostasis in simultaneous bilateral TKA, contributing to reduced postoperative blood loss without increasing complications. ORC may be a valuable adjunct for blood loss management in TKA.