A Novel Thromboplastin-Based Rat Model of Ischemic Stroke.

Irina V Ostrova,Sergei N Kalabushev,Ivan A Ryzhkov,Zoya I Tsokolaeva

doi:10.3390/brainsci11111475

Abstract

The thromboembolic ischemia model is one of the most applicable for studying ischemic stroke in humans. The aim of this study was to develop a novel thromboembolic stroke model, allowing, by affordable tools, to reproduce cerebral infarction in rats. In the experimental group, the left common carotid artery, external carotid artery, and pterygopalatine branch of maxillary artery were ligated. A blood clot that was previously formed (during a 20 min period, in a catheter and syringe, by mixing with a thromboplastin solution and CaCl2) was injected into the left internal carotid artery. After 10 min, the catheter was removed, and the incision was sutured. The neurological status of the animals was evaluated using a 20-point scale. Histological examination of brain tissue was performed 6, 24, 72 h, and 6 days post-stroke. All groups showed motor and behavioral disturbances 24 h after surgery, which persisted throughout the study period. A histological examination revealed necrotic foci of varying severity in the cortex and subcortical regions of the ipsilateral hemisphere, for all experimental groups. A decrease in the density of hippocampal pyramidal neurons was revealed. Compared with existing models, the proposed ischemic stroke model significantly reduces surgical time, does not require an expensive operating microscope, and consistently reproduces brain infarction in the area of the middle cerebral artery supply.

Highlights

One of the main requirements for the development of experimental models of cerebrovascular disease is the maximal relevance for real-life clinical practice
Changes in the blood flow properties have been studied on thromboembolic models, which should be taken into account when developing both reperfusion and neuroprotective approaches to the treatment of ischemic stroke [5]
One-way ANOVA revealed that physiological parameters as well as the body weight measured before surgery did not differ significantly between groups (p > 0.05) (Table 1)

Summary

Introduction

One of the main requirements for the development of experimental models of cerebrovascular disease is the maximal relevance for real-life clinical practice. The choice of the most appropriate model can be crucial for investigating potential treatment strategies for stroke and its sequelae [1]. In most cases, results from a sudden arterial occlusion (most commonly of the middle cerebral artery) by a thrombus or embolus. Embolic occlusion of the middle cerebral artery (MCAO), with an autologous or heterologous blood clot in rodents, is one of the methods to model focal and multifocal cerebral ischemia, and is highly consistent with the pathogenesis of ischemic stroke in humans [2,3,4]. Changes in the blood flow properties have been studied on thromboembolic models, which should be taken into account when developing both reperfusion and neuroprotective approaches to the treatment of ischemic stroke [5]. The possibility of testing new thrombolytic agents is another important advantage of these models [3,4]

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Discussion

Conclusion