A Novel Rat Model of Venous Hypertensive Myelopathy Produced by Arteriovenous Bypass Plus Venous Stenosis-Reference-Cited by-同舟云学术

A Novel Rat Model of Venous Hypertensive Myelopathy Produced by Arteriovenous Bypass Plus Venous Stenosis

Published:2024-04-15 Issue: Volume: Page:
ISSN:0148-396X
Container-title:Neurosurgery
language:en
Short-container-title:

Author:

Wang Yinqing¹²³,Yang Chengbin¹,Wang Jiachen⁴,Wei Mengping⁵,Xu Qing⁶,Wang Zhanjing⁷,Tu Tianqi¹,Fan Yuxiang¹,Song Zihao¹,Duan Wanru¹³,Chen Chunmei²,Zhang Hongqi¹,Ma Yongjie¹^ORCID

Affiliation:

1. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China;

2. Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China;

3. Lab of Spinal Cord Injury and Functional Reconstruction, China International Neuroscience Institute (China-INI), Beijing, China;

4. The First Clinical Medical College, Capital Medical University, Beijing, China;

5. School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China;

6. Core Facilities for Electrophysiology, Core Facilities Center, Capital Medical University, Beijing, China;

7. Center for Medical Experiments and Testing, Capital Medical University, Beijing, China

Abstract

BACKGROUND AND OBJECTIVES: Venous hypertensive myelopathy (VHM), mainly induced by the spinal dural arteriovenous fistula, is a congestive spinal cord injury that currently has no appropriate animal model available in preclinical research. METHODS: Sprague Dawley rats (280-320 g) were used. The rats were divided into 3 groups: (1) Group 1, which underwent renal artery-dorsal spinal venous bypass (AVB group); (2) Group 2, which underwent renal artery-dorsal spinal venous bypass and drainage vein stenosis (AVB/VS group); and (3) Control group, with T13 dorsal vein ligation. The success of the model was assessed using Doppler ultrasound and 7.0-T magnetic resonance imaging. Transmission electron microscopy, histochemistry, proteomics, and western blot analysis were used to evaluate ultrastructural, pathological, and molecular features in the spinal cord and cerebrospinal fluid (CSF). RESULTS: The success rate of the arteriovenous bypass was 100% at 5 days and 83% at 2 weeks. The locomotor assessment showed decreased lower extremity strength in the AVB/VS group (P = .0067), whereas unremarkable changes were found in the AVB and Control groups. Histochemical staining suggested a 2-fold expansion of the dorsal spinal vein in the AVB/VS group, which was lower than that in the AVB group (P < .05); however, the former displayed greater myelin and neuronal damage (P < .05) and slight dilatation of the central canal (P > .05). Proteomics analysis revealed that the complement and coagulation cascade pathways were upregulated in the CSF of AVB/VS rats, whereas the C3 level was elevated both in the CSF and bilateral spinal cord. Furthermore, overexpression of C3, ITGB2, and CD9 in the spinal cord was confirmed by immunoblotting. CONCLUSION: These findings suggest that the AVB/VS model can effectively mimic the clinical and molecular characteristics of VHM. Furthermore, they suggest that impaired deep intramedullary venous drainage is the key reason for the VHM.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference28 articles.

1. Arteriovenous fistulae of the meninges draining into the spinal veins. A histological study of 28 cases;Benhaiem;Acta Neuropathol.,1983

2. Spinal dural arteriovenous fistulas: a congestive myelopathy that initially mimics a peripheral nerve disorder;Jellema;Brain J Neurol.,2006

3. The pathophysiology of spinal vascular malformations;Aminoff;J Neurol Sci.,1974

4. [Subacute necrotic myelitis (Foix-Alajouanine disease) 1];Hirayama;Shinkei Kenkyu No Shimpo.,1970

5. Spinal dural arteriovenous fistula: the pathology of venous hypertensive myelopathy;Hurst;Neurology.,1995