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Many published literature sources have described the histopathological characteristics of post-traumatic syringomyelia (PTS). However, three-dimensional (3D) visualization studies of PTS have been limited due to the lack of reliable 3D imaging techniques. In this study, the imaging efficiency of propagation-based synchrotron radiation microtomography (PB-SRµCT) was determined to detect the 3D morphology of the cavity and surrounding microvasculature network in a rat model of PTS. The rat model of PTS was established using the infinite horizon impactor to produce spinal cord injury (SCI), followed by a subarachnoid injection of kaolin to produce arachnoiditis. PB-SRµCT imaging and histological examination, as well as fluorescence staining, were conducted on the animals at the tenth week after SCI. The 3D morphology of the cystic cavity was vividly visualized using PB-SRµCT imaging. The quantitative parameters analyzed by PB-SRµCT, including the lesion and spared spinal cord tissue area, the minimum and maximum diameters in the cystic cavity, and cavity volume, were largely consistent with the results of the histological assessment. Moreover, the 3D morphology of the cavity and surrounding angioarchitecture could be simultaneously detected on the PB-SRµCT images. This study demonstrated that high-resolution PB-SRµCT could be used for the 3D visualization of trauma-induced spinal cord cavities and provides valuable quantitative data for cavity characterization. PB-SRµCT could be used as a reliable imaging technique and offers a novel platform for tracking cavity formation and morphological changes in an experimental animal model of PTS. [ABSTRACT FROM AUTHOR]

microRNAs are a novel set of small, non-protein-coding nucleotide RNAs that negatively regulate the expression of target mRNAs. miRNA-21 is a microRNA that is highly enriched in endothelial cells. miRNA-21 has been shown to be a potential pro-angiogenic factor in some biological systems. Our previous study showed that the expression of miRNA-21 was up-regulated after spinal cord injury. However, the effect of miRNA-21 on angiogenesis in the spinal cord was unclear. In this study, to understand the role of miRNA-21 on injured endothelial cells exclusively, an oxygen and glucose deprivation model of endothelial cells was constructed, and the up-regulation of miRNA-21 was discovered in this model. An increased level of miRNA-21 by mimics promoted the survival, migration and tube formation of endothelial cells, which simultaneously inhibited tissue inhibitor of metalloproteinase-3 (TIMP3) expression and promoted matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) expression and secretion. A decreased level of miRNA-21 by antagomir exerted an opposite effect. As is well known, survival, migration and tube formation of endothelial cells are necessary prerequisites for angiogenesis after injury. TIMP3 was validated as a direct target of miRNA-21 by dual-luciferase reporter assay. Silencing with small interfering RNA against TIMP3 promoted tube formation and increased MMP2 and MMP9 expression at the protein level. In vivo, we found that decreased levels of miRNA-21 inhibited angiogenesis after spinal cord injury in rats using synchrotron radiation micro-computed tomography. In summary, these findings suggest that miRNA-21 has a protective effect on angiogenesis by reducing cell death and promoting cell survival, migration and tube formation via partially targeting the TIMP3 by potentially regulating MMP2 and MMP9. TIMP3 is a functional target gene. Identifying the role of miRNA-21 in the protection of angiogenesis might offer a novel therapeutic target for secondary spinal cord injury, in which angiogenesis is indispensable. [ABSTRACT FROM AUTHOR]

Vascular injury following spinal cord injury (SCI) can significantly exacerbate secondary SCI and result in neurological dysfunction. Strategies targeting angiogenesis have demonstrated potential in enhancing functional recovery post-SCI. In the context of angiogenesis, the CD146+ and CD271+ subpopulations of mesenchymal stem cells (MSCs) have been recognized for their angiogenic capabilities in tissue repair. Small extracellular vesicles (sEVs) derived from MSCs are nanoscale vesicles containing rich bioactive components that play a crucial role in tissue regeneration. However, the precise role of sEVs derived from CD146+CD271+ UCMSCs (CD146+CD271+ UCMSC-sEVs) in SCI remain unclear. In this study, CD146+CD271+ UCMSC-sEVs were non-invasively administered via intranasal delivery, demonstrating a significant capacity to stimulate angiogenesis and improve functional recovery in mice following SCI. Furthermore, in vitro assessments revealed the effective enhancement of migration and tube formation capabilities of the murine brain microvascular endothelial cell line (bEnd.3) by CD146+CD271+UCMSC-sEVs. MicroRNA array analysis confirmed significant enrichment of multiple microRNAs within CD146+CD271+ UCMSC-sEVs. Subsequent in vivo and in vitro experiments demonstrated that CD146+CD271+ UCMSC-sEVs promote enhanced angiogenesis and improved functional recovery mediated by miR-27a-3p. Further mechanistic studies revealed that miR-27a-3p sourced from CD146+CD271+ UCMSC-sEVs enhances migration and tube formation of bEnd.3 cells in vitro by suppressing the expression of Delta Like Canonical Notch Ligand 4 (DLL4), thereby promoting angiogenesis in vivo. Collectively, our results demonstrate that a crucial role of CD146+CD271+ UCMSC-sEVs in inhibiting DLL4 through the transfer of miR-27a-3p, which leads to the promotion of angiogenesis and improved functional recovery after SCI. [Display omitted] • Intranasal delivery of CD146+CD271+ UCMSC-sEVs can effectively promote angiogenesis and functional recovery after SCI. • miR-27a-3p mediates the effects of CD146+CD271+ UCMSC-sEVs on improving functional recovery and angiogenesis after SCI. • CD146+CD271+ UCMSCs-sEVs promote angiogenesis via the miR-27a-3p/DLL4 pathway. [ABSTRACT FROM AUTHOR]

Study Design: An advanced imaging of vasculature with synchrotron radiation X-ray in a rat model.Objective: To develop the potential for quantitative assessment of vessel network from two-dimensional (2D) to 3D visualization by synchrotron radiation X-ray phase contrast tomography (XPCT) in rat spinal cord model.Summary Of Background Data: Investigation of microvasculature contributes to the understanding of pathological development of spinal cord injury. A few of X-ray imaging is available to visualize vascular architecture without usage of angiography or invasive casting preparation.Methods: A rat spinal cord injury model was produced by modified Allen method. Histomorphometric detection was simultaneously analyzed by both histology and XPCT from 2D to 3D visualization. The parameters including tissue lesion area, microvessel density, vessel diameter, and frequency distribution of vessel diameter were evaluated.Results: XPCT rendered the microvessels as small as capillary scale with a pixel size of 3.7 μm. It presented a high linear concordance for characterizing the 2D vascular morphometry compared with the histological staining (r = 0.8438). In the presence of spinal cord injury model, 3D construction quantified the significant angioarchitectural deficiency in the injury epicenter of cord lesion (P<0.01).Conclusion: XPCT has a great potential to detect the smallest vascular network with pixel size up to micron dimension. It is inferred that the loss of abundant microvessels (≤40 μm) is responsible for local ischemia and neural dysfunction. XPCT holds a promise for morphometric analysis from 2D to 3D imaging in experimental model of neurovascular disorders.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Study Design: The micro-computed tomography (micro-CT) was applied to assess the effect of tetramethylpyrazine (TMP) on experimental spinal cord injury (SCI).Objective: The aim of the study was to explore the therapeutic effect of TMP on a rat SCI model using micro-CT.Summary Of Background Data: SCI is a devastating event and always accompanied by severe vascular injury. Promoting angiogenesis after SCI has recently been recognized as a potential way to enhance the neurological function recovery. How the TMP promotes angiogenesis and improved locomotor function recovery after SCI has, however, not been fully clarified. In this study, we used micro-CT to evaluate the effect on the microvasculature changes after TMP treatment.Methods: The contusion SCI model was induced in rats by a modified Allen's impact method. In the TMP treatment group, rats were injected intraperitoneally with TMP. The control group was treated with saline. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan score. Histology was employed to examine the pathological changes and quantified at 28 days after injury. Spinal cord vessel network and angiogenesis were assessed using micro-CT.Results: Angiogenesis was increased in groups treated with TMP compared with rat in the control groups (P < 0.05). Micro-CT vividly depicted the three-dimensional morphology changes of the spinal cord microvasculature after injury and demonstrated more vessels number, vessel volume fraction, and vessel connectivity value in the groups treated with TMP than in the control groups (P < 0.05). In addition, the injury-induced lesion area in TMP group was attenuated in comparison with control groups. Similarly, neurological functions were greatly improved in groups treated with TMP compared with rats in the control groups.Conclusion: Micro-CT is useful for detecting angiogenesis after SCI. TMP therapy reduced the neuronal loss, promoted angiogenesis, and exerted a positive effect on neurological function recovery after SCI.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]