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...

Full description

Bibliographic Details
Main Authors: Katarzyna Pawletko, Halina Jędrzejowska-Szypułka, Katarzyna Bogus, Alessia Pascale, Foroogh Fahmideh, Nicoletta Marchesi, Aniela Grajoszek, Edyta Olakowska, Jarosław Jerzy Barski
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/12/1671
_version_ 1797461171245154304
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.
first_indexed 2024-03-09T17:15:37Z
format Article
id doaj.art-c4cb6df85d904665b24a94b1cde40166
institution Directory Open Access Journal
issn 2076-3425
language English
last_indexed 2024-03-09T17:15:37Z
publishDate 2022-12-01
publisher MDPI AG
record_format Article
series Brain Sciences
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
work_keys_str_mv AT katarzynapawletko anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT halinajedrzejowskaszypułka anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT katarzynabogus anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT alessiapascale anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT forooghfahmideh anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT nicolettamarchesi anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT anielagrajoszek anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT edytaolakowska anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT jarosławjerzybarski anovelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT katarzynapawletko novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT halinajedrzejowskaszypułka novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT katarzynabogus novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT alessiapascale novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT forooghfahmideh novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT nicolettamarchesi novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT anielagrajoszek novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT edytaolakowska novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies
AT jarosławjerzybarski novelimprovedthromboembolismbasedratstrokemodelthatmeetsthelateststandardsinpreclinicalstudies