A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies
The animal thromboembolic model of ischemia perfectly mimics human ischemic stroke which remains the leading cause of disability and mortality in humans. The development of new treatment strategies was therefore imperative. The purpose of this study is to improve the thromboembolic stroke model in r...
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2022-12-01
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author | Katarzyna Pawletko Halina Jędrzejowska-Szypułka Katarzyna Bogus Alessia Pascale Foroogh Fahmideh Nicoletta Marchesi Aniela Grajoszek Edyta Olakowska Jarosław Jerzy Barski |
author_facet | Katarzyna Pawletko Halina Jędrzejowska-Szypułka Katarzyna Bogus Alessia Pascale Foroogh Fahmideh Nicoletta Marchesi Aniela Grajoszek Edyta Olakowska Jarosław Jerzy Barski |
author_sort | Katarzyna Pawletko |
collection | DOAJ |
description | The animal thromboembolic model of ischemia perfectly mimics human ischemic stroke which remains the leading cause of disability and mortality in humans. The development of new treatment strategies was therefore imperative. The purpose of this study is to improve the thromboembolic stroke model in rats in order to design experiments that use motor tests, and are in accordance with the 3R principles to prevent complications and maintain the same size of the infarct repeatedly. Tail vein dye application, a protective skull mask and a stress minimization protocol were used as additional modifications to the animal stroke model. These modifications significantly minimized the pain and stress severity of the procedures in this model. In our experimental group of Long-Evans rats, a photo-induced stroke was caused by the application of a photosensitive dye (Rose Bengal) activated with white-light irradiation, thus eliminating the need to perform a craniotomy. The animals’ neurological status was evaluated using a runway elevated test. Histological examination of the brain tissue was performed at 12, 24 and 48 h, and seven days post-stroke. Tissue examination revealed necrotic foci in the cortex and the subcortical regions of the ipsilateral hemisphere in all experimental groups. Changes in the area, width and depth of the necrotic focus were observed over time. All the experimental groups showed motor disturbances after stroke survival. In the proposed model, photochemically-induced stroke caused long-term motor deficits, showed high reproducibility and low mortality rates. Consequently, the animals could participate in motor tests which are particularly suitable for assessing the efficacy of neuro-regenerative therapies, while remaining in line with the latest trends in animal experimental design. |
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spelling | doaj.art-c4cb6df85d904665b24a94b1cde401662023-11-24T13:39:43ZengMDPI AGBrain Sciences2076-34252022-12-011212167110.3390/brainsci12121671A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical StudiesKatarzyna Pawletko0Halina Jędrzejowska-Szypułka1Katarzyna Bogus2Alessia Pascale3Foroogh Fahmideh4Nicoletta Marchesi5Aniela Grajoszek6Edyta Olakowska7Jarosław Jerzy Barski8Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandDepartment of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandDepartment of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandDepartment of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, ItalyDepartment of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, ItalyDepartment of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, ItalyDepartment of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandDepartment of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandDepartment of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, PolandThe animal thromboembolic model of ischemia perfectly mimics human ischemic stroke which remains the leading cause of disability and mortality in humans. The development of new treatment strategies was therefore imperative. The purpose of this study is to improve the thromboembolic stroke model in rats in order to design experiments that use motor tests, and are in accordance with the 3R principles to prevent complications and maintain the same size of the infarct repeatedly. Tail vein dye application, a protective skull mask and a stress minimization protocol were used as additional modifications to the animal stroke model. These modifications significantly minimized the pain and stress severity of the procedures in this model. In our experimental group of Long-Evans rats, a photo-induced stroke was caused by the application of a photosensitive dye (Rose Bengal) activated with white-light irradiation, thus eliminating the need to perform a craniotomy. The animals’ neurological status was evaluated using a runway elevated test. Histological examination of the brain tissue was performed at 12, 24 and 48 h, and seven days post-stroke. Tissue examination revealed necrotic foci in the cortex and the subcortical regions of the ipsilateral hemisphere in all experimental groups. Changes in the area, width and depth of the necrotic focus were observed over time. All the experimental groups showed motor disturbances after stroke survival. In the proposed model, photochemically-induced stroke caused long-term motor deficits, showed high reproducibility and low mortality rates. Consequently, the animals could participate in motor tests which are particularly suitable for assessing the efficacy of neuro-regenerative therapies, while remaining in line with the latest trends in animal experimental design.https://www.mdpi.com/2076-3425/12/12/1671focal ischemic strokephotothrombosisanimal modelmotor testpenumbra |
spellingShingle | Katarzyna Pawletko Halina Jędrzejowska-Szypułka Katarzyna Bogus Alessia Pascale Foroogh Fahmideh Nicoletta Marchesi Aniela Grajoszek Edyta Olakowska Jarosław Jerzy Barski A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies Brain Sciences focal ischemic stroke photothrombosis animal model motor test penumbra |
title | A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies |
title_full | A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies |
title_fullStr | A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies |
title_full_unstemmed | A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies |
title_short | A Novel Improved Thromboembolism-Based Rat Stroke Model That Meets the Latest Standards in Preclinical Studies |
title_sort | novel improved thromboembolism based rat stroke model that meets the latest standards in preclinical studies |
topic | focal ischemic stroke photothrombosis animal model motor test penumbra |
url | https://www.mdpi.com/2076-3425/12/12/1671 |
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