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Abstract
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A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats

Published: May 22, 2019
doi:
10.3791/58875
, , , , , , , , ,
1Department of Anesthesiology and Critical Care, Soroka University Medical Center, Faculty of Health Sciences,Ben-Gurion University of the Negev, 2Department of Neurosurgery, Soroka University Medical Center, Faculty of Health Sciences,Ben-Gurion University of the Negev, 3Department of Biophysics and Biochemistry, Faculty of Biology, Ecology, and Medicine,Oles Honchar Dnipro National University

Summary

Here we present a protocol to induce post-stroke depression in rats by occluding the middle cerebral artery via the internal carotid artery. We use the Porsolt forced swim test and the sucrose preference test to confirm and evaluate induced depressive moods.

Abstract

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Introduction

Stroke is fourth on the list of death-perpetrating diseases in the United States1,2,3, while it causes the majority of disabilities in adults in developed countries4; this makes stroke a leading contender among the world's most significant health issues. Normalcy in stroke-surviving patients is rare, with about 15%-40% of survival victims suffering permanent disability, 20% requiring institutional care 3 months after stroke onset5, and about a third of 6-month survivals needing others to help them live through each day6. Stroke reportedly also accounts for the rising national health expenditures7. Estimates from the American Heart Association has stroke-related costs in the United States at over $50 billion in 20108.

Not only does stroke cause individuals' long-term damages, but some survivors tend to suffer emotional and behavioral disorders, such as dementia, fatigue, anxiety, depression, delirium, and aggression9,10,11,12,13,14. The most recurrent psychological sequel after a stroke is post-stroke depression (PSD), diagnosed in about 40%-50% of survivals15,16,17. Stroke-induced depression results in increased morbidity and mortality18,19,20,21,22. The pathophysiology of PSD is not known completely, but it is apparently caused by multiple factors and is linked to disability, cognitive impairment, and lesion site23.

The rat model of focal brain ischemia, created by MCAO, is the most widespread animal model of stroke24,25,26,27. In demonstrating the induction of PSD in rats by occluding the MCA via the ICA, techniques that minimize mortality and variability in the MCAO model are employed28.

The primary objective of this protocol is to outline the steps for inducing PSD in rats by occluding the MCA via the ICA, a modified model of MCAO, which reduces mortality and the outcome of variability28. Specific aims include performing neurological and histological examinations (determining the neurological severity score [NSS], the volume of the infarction zone, and brain edema) to verify the efficacy of MCAO and using behavioral tests to examine the influence of this MCAO procedure on the development of emotional disorders, mainly PSD.

Protocol

The Animal Care Committee of the Ben-Gurion University of the Negev, Israel approved all treatment and testing procedures used in this protocol. 1. Preparation of Rats for the Experimental Procedure NOTE: Select adult male Sprague-Dawley rats weighing 300-350 g. House the rats, four per cage, in a vivarium at 22 °C and 40% humidity, with a reversed 12 h light/dark cycle (lights off at 8:00 a.m.) and unlimited access to food and wate…

Representative Results

Histological findings (Table 1) revealed a statistically significant infarct volume as a percentage of total brain (p < 0.0001) post-MCAO when compared to animals in the sham-control group. Also reported was a statistically significant brain edema when the evaluation from the experimental group (p < 0.0003) was put side by side with that of the sham-control group. The NSS scores obtaine…

Discussion

One of the ways in which the MCAO technique presented here could be deemed safer than the original MCAO model is illustrated by the fact that the ECA and its branches, including the occipital artery, the terminal lingual, and the maxillary artery, are not compromised when occluding the MCA via the ICA. The original MCAO model's offset of the ECA (and its branches), by distally dissecting and coagulating them46, causes impaired mastication, owing to a compromise to the vascular supply to mastic…

Offenlegungen

The authors have nothing to disclose.

Acknowledgements

We thank Professor Olena Severynovska of the Department of Physiology, Faculty of Biology, Ecology, and Medicine, Oles Honchar Dnipro University, Dnipro, Ukraine for her support and helpful contributions to our discussions. The data obtained are part of R.K.’s PhD thesis.

Materials

Absorbent pad – – –
Black lusterless perspex box – – (120 cm × 60 cm × 60 cm), divided into a 25% central zone and the surrounding border zone
Bottles Techniplast ACBT0262SU 150 ml bottles filled with 100 ml of water and 100 ml 1%(w/v) sucrose solution
Electric Shock Heat System Ultasonic Inc. – –
Horizon-XL Mennen Medical Ltd
Imaging System Kodak – For imaging and quantification
Monofilament – – –
Paper towels Pharmacy – Dry towels used for keeping rats dry after immersing them in water
Pexiglass cylinder – – a 100 cm tall and 40 cm in diameter cylinder used for carrying out the forced swim test
Purina Chow Purina 5001 Rodent laboratory chow given to rats, mice and hamster is a life-cycle nutrition that has been used in biomedical researc for over 5 decades. Provided to rats ad libitum in this experiment
Rat Cages Techniplast 2000P Conventional housing for rodents. Was used for housing rats throughout the experiment
Scanner  Canon CanoScan 4200F –
Video Camera ETHO-VISION (Noldus) – Digital video camera for high definition recording of rat behavior under open field test
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Referenzen

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Tags

Middle Cerebral Artery OcclusionPost-stroke DepressionRat ModelNeurological Severity ScoreInfarct VolumeSucrose Preference TestForced Swim Test

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Kuts, R., Melamed, I., Shiyntum, H. N., Frank, D., Grinshpun, J., Zlotnik, A., Brotfain, E., Dubilet, M., Natanel, D., Boyko, M. A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats. J. Vis. Exp. (147), e58875, doi:10.3791/58875 (2019).
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