SRμCT Reveals 3D Microstructural Alterations of the Vascular and Neuronal Network in a Rat Model of Chronic Compressive Thoracic Spinal Cord Injury

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 c ord 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.

Ultrafast Doppler imaging and Ultrasound Localization Microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

“…Both approaches provided similar, statistically equivalent results, validating the use of ULM for the quanti cation of structural vascular alterations. Moreover, the observed reduced blood vessel density is consistent with previous reports on hemorrhage and vascular plasticity (Jiang et al, 2020).…”

“…As previously quanti ed using micro-computed tomography (Cao et al, 2015;Jiang et al, 2020)), and con rmed here, the shape of the CSA is altered, giving rise to a non-orthogonal ascending ow. The number of branches of the CSA and its diameter are also reduced (Ni et al, 2018;Jiang et al, 2020). Our statistical analysis proves that these alterations are correlated with increased tortuosity.…”

Bone Marrow Mesenchymal Stem Cell-Derived Exosome-Educated Macrophages Promote Functional Healing After Spinal Cord Injury

“…It permits imaging of soft tissue such as the vasculature visualization without contrast agents’ perfusion. Our research group has already started to apply SRμCT to visualize the vascular and neuronal networks in a rat model of chronic compressive thoracic SCI ( Jiang et al, 2020 ). This method enables visualization of the 3D structure of the entire neural and vascular network of the spinal cord.…”

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport

“…Frozen brain tissues were sliced into 10 μm sections and prepared for immunostaining as described previously [ 30 ]. The primary antibodies were rabbit anti-NeuN (1:300, Invitrogen, USA), mouse anti-GLUT1 and mouse anti-GLUT3 antibodies (1:400, Santa Cruz, USA).…”