Abstract
The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal-spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression.
Highlights
Chronic progressive spinal cord compression, which results from progressive stenosis of the spinal canal, is very common in clinical settings, accounting for 30%– 80% of cases of nontraumatic spinal cord injury [1,2,3]
Since very few investigations have focused on chronic thoracic spinal cord compression injuries, far less is known about their course, treatment response, and recovery potential
Synchrotron radiation microtomography (SRμCT) has been recognized as a powerful tool to explore the 3D structure of biospecimens across a large spatial range, down to submicron resolutions [2026]
Summary
Chronic progressive spinal cord compression, which results from progressive stenosis of the spinal canal, is very common in clinical settings, accounting for 30%– 80% of cases of nontraumatic spinal cord injury [1,2,3]. Recent studies have provided evidence that disruption of neurons and vasculature should be acknowledged as concurrent events in neurological disorders [14] This approach suggests that the responses of the vascular and neuronal networks could be coordinated, indicating the crucial importance of analyzing these responses simultaneously. The 3D microstructural morphological changes in the vascular and neuronal networks during thoracic spinal cord compression have not been fully elucidated. 3D investigations of alterations in the neuronal and vascular networks would undoubtedly be helpful for gaining further insight into pathological processes and for developing effective strategies for the treatment of chronic thoracic spinal cord compression. SRμCT was used to characterize and quantify the microstructural features of the vascular and neuronal network changes in response to chronic thoracic spinal cord compression
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