Dataset Information

Three-dimensional imaging of microvasculature in the rat spinal cord following injury.

ABSTRACT: Research studies on the three-dimensional (3D) morphological alterations of the spinal cord microvasculature after injury provide insight into the pathology of spinal cord injury (SCI). Knowledge in this field has been hampered in the past by imaging technologies that provided only two-dimensional (2D) information on the vascular reactions to trauma. The aim of our study is to investigate the 3D microstructural changes of the rat spinal cord microvasculature on day 1 post-injury using synchrotron radiation micro-tomography (SRμCT). This technology provides high-resolution 3D images of microvasculature in both normal and injured spinal cords, and the smallest vessel detected is approximately 7.4 μm. Moreover, we optimized the 3D vascular visualization with color coding and accurately calculated quantitative changes in vascular architecture after SCI. Compared to the control spinal cord, the damaged spinal cord vessel numbers decreased significantly following injury. Furthermore, the area of injury did not remain concentrated at the epicenter; rather, the signs of damage expanded rostrally and caudally along the spinal cord in 3D. The observed pathological changes were also confirmed by histological tests. These results demonstrate that SRμCT is an effective technology platform for imaging pathological changes in small arteries in neurovascular disease and for evaluating therapeutic interventions.

SUBMITTER: Cao Y

PROVIDER: S-EPMC4518284 | biostudies-other | 2015

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundAstrocytes act as immune effector cells with the ability to produce a wide array of chemokines and cytokines in response to various stimuli. Macrophage migration inhibitory factor (MIF) is inducibly expressed in injured spinal cord contributing to excessive inflammation that affects motor functional recovery. Unknown is whether MIF can facilitate inflammatory responses through stimulating release of chemokines from astrocytes following spinal cord injury.MethodsFollowing the establishment of the contusion spinal cord injury rat model, the correlation of chemokine (C-C motif) ligand 5 (CCL5) expression with that of MIF was assayed by Western blot, ELISA, and immunohistochemistry. Immunoprecipitation was used to detect MIF interaction with membrane CD74 receptor. Intracellular signal transduction of MIF/CD74 axis was analyzed by transcriptome sequencing of primary astrocytes and further validated by treatment of various inhibitors. The effects of CCL5 released by astrocytes on macrophage migration were performed by transwell migration assay. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale.ResultsThe protein levels of chemokine CCL5/RANTES were remarkably increased in the astrocytes of rat injured spinal cord, in parallel with the expression of MIF. Treatment of MIF inhibitor 4-IPP in the lesion sites resulted in a significant decrease of CCL5 protein levels. In vitro study revealed MIF was capable of facilitating CCL5 production of astrocytes through interaction with CD74 membrane receptor, and knockdown of this receptor attenuated such effects. Production of CCL5 in astrocytes was significantly blocked by inhibitor of c-Jun N-terminal kinase, rather than by those of ERK and P38. Recombinant CCL5 protein was found to be more effective in promoting migration of M2- compared to M1-type macrophages.ConclusionCollectively, these data reveal a novel function of MIF in regulation of CCL5 release from astrocytes, which in turn favors for recruitment of inflammatory cells to the injured site of the spinal cord, in association with activation of excessive inflammation.

Dataset Information

Three-dimensional imaging of microvasculature in the rat spinal cord following injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets