Elsevier

Neuroscience

Volume 416, 15 September 2019, Pages 41-49
Neuroscience

RESEARCH ARTICLE
Establishment of a Rat Model of Superior Sagittal-Sinus Occlusion and Recanalization via a Thread-Embolism Method

https://doi.org/10.1016/j.neuroscience.2019.07.044Get rights and content

Highlights

  • A model of acute occlusion and recanalization of the SSS has been established.

  • Brain edema after SSS occlusion is slightly reversible.

  • Compensatory effect of venous collateral circulation can improve brain edema.

  • Early removal of the SSS occlusion can improve cerebral blood circulation.

Abstract

There are many uncontrollable factors in the pathogenesis of cerebral venous sinus thrombosis (CVST). In order to further explore the pathophysiology and morphology of CVST, it is necessary to establish a highly compatible CVST animal model that can standardize the site and stage of venous thrombosis. The present study employed the insertion of a self-made thread embolism into the superior sagittal sinus (SSS) to establish a rat model of SSS occlusion that emulates CVST. The thread embolism was removed after 6 h of SSS occlusion in order to achieve recanalization. After successful preparation of the model, the cerebral blood flow (CBF) status and ultrastructural changes of the blood–brain barrier (BBB) were monitored. This CVST model was able to achieve continuously high occlusion of SSS. The parasagittal venous-collateral circulation underwent extensive compensation and recombination, which alleviated blood flow stasis and brain tissue hypoxia caused by restricted reflux. Removing SSS occlusion significantly improved cerebral circulation, reduced brain edema, and accelerated the receding of brain edema. This study established a new model of acute occlusion and recanalization of SSS in rats via a thread-embolism method, which standardized the ischemic site and stage of venous thrombosis. In addition, our study suggests that promoting collateral circulation may be a potential treatment for promoting brain protection.

Introduction

Cerebral venous sinus thrombosis (CVST) is a rare cerebral venous-system disease that accounts for only 0.5%–1.0% of the causes of stroke (Bousser and Ferro, 2007). CVST patients exhibit clinical manifestations that lack specificity, and most patients have insidious onsets of the disease, the combination of which contributes to considerable difficulties in CVST clinical research and treatment (Einhaupl et al., 2010, Coutinho et al., 2014). In order to further explore the pathophysiology and morphology of CVST, it is necessary to establish a highly compatible CVST animal model that can standardize the site and stage of venous thrombosis.

In human CVST, the superior sagittal sinus (SSS) is the most common anatomical site of the source of pathology (Ferro et al., 2004). A variety of SSS thrombosis models have been established, including SSS ligation (Gotoh et al., 1993, Miyamoto et al., 2001), injection of kaolin–cephalin suspension (Ungersbock et al., 1993), occlusion SSS by a self-made plastic graft (Yang et al., 2012), and application of ferric chloride (Rottger et al., 2005) or photochemicals (Chen et al., 2015) for inducing thrombosis. However, most of these models are difficult to accurately control ischemia duration, which may accompany spontaneous recanalization or permanent occlusion of the SSS. After CVST occurrence, blood-flow stasis and tissue hypoxia can lead to the formation of brain edema (Sagoo et al., 2017). However, clinical observations have shown that the outcome of an ischemic lesion is independent of the degree of sinus occlusion (Rottger et al., 2005); the compensatory effect of the intracranial venous system may play an important role in this process. However, the specific mechanism underlying this putative compensatory effect remains to be elucidated.

In the present study, acute SSS occlusion was induced by inserting a self-made thread embolism into the SSS of rats. The occlusion duration was precisely regulated by the latency until removal, such that the recanalization of the SSS could be easily managed. The stability and reliability of this model were confirmed by laser-speckle contrast imaging (LSCI), histopathology, and microscopy over the course of 14 days. This model may provide a platform for further elucidation and development of treatments for the pathophysiology of CVST.

Section snippets

Animal preparation

This experiment was approved by the Fujian Medical University Ethics Committee and was in accordance with the Guide for the Care and Use of Laboratory Animals (Institute for Laboratory Animal Research, National Research Council. Washington, DC: National Academy Press, 1996). Male Sprague–Dawley rats (280–300 g, Animal Experimental Center of 900 Hospital of the Joint Logistics Team, Fuzhou, China) were used in this study. Animals were maintained in a standard environment of 26–28 °C, a 10-h

Transient changes of CBF

The CBF immediately declined to different degrees after SSS occlusion in the observation region, especially for the internal CBF in the SSS that almost completely blocked (Fig. 3B). However, compared with that at post-occlusion, the CBF was significantly improved after recanalization (P < 0.001) (Fig. 3C and D). The CBF in the SSS did not completely recover immediately, while the CBF in the arteries and microcirculation exceeded that of the baseline, possibly because of the increasing

Discussion

As early as 1989, Longa et al. established the first reversible middle-cerebral-artery occlusion model via insertion of a self-made nylon thread into the external carotid artery of rats (Longa et al., 1989). Since then, there have been many improved methods that have aimed to increase the stability of this model (Fluri et al., 2015). These models, which exhibit the characteristics of accurate ischemic sites and stages and are amenable for inducing recanalization, have been widely used in basic

Acknowledgments

This work was financially supported by the Startup Fund for scientific research at Fujian Medical University for Wei Wang (no. 2017XQ2049); Major Science and Technology Projects of General Logistics Department of Chinese People's Liberation Army (no. AHJ14J001); Natural Science Foundation of Fujian Province Grant (no. 2017 J01323).

Contributors

WW and MSW were responsible for the study concept and design. WW, MSW, XWM, LSX, LRH, LZF, LQH, and YGC performed the experiments. WW and MSW were responsible for the data analyses and interpretations. WW and MSW drafted the manuscript. WSS and XL critically reviewed the manuscript.

Conflicts of interest

The authors declare that they have no conflicts interests.

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    These authors contributed equally to this work.

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