Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology

Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of t...

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Main Authors: Takamasa Mizoguchi, Ayumi Maki, Yuno Nakase, Mayu Okita, Yuina Minami, Misa Fukunaga, Motoyuki Itoh
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025000371
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author Takamasa Mizoguchi
Ayumi Maki
Yuno Nakase
Mayu Okita
Yuina Minami
Misa Fukunaga
Motoyuki Itoh
author_facet Takamasa Mizoguchi
Ayumi Maki
Yuno Nakase
Mayu Okita
Yuina Minami
Misa Fukunaga
Motoyuki Itoh
author_sort Takamasa Mizoguchi
collection DOAJ
description Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of this condition, therapeutic options remain limited, with a pressing challenge being the development of treatments aimed at restoring neurological function. In this study, we leveraged zebrafish, renowned for their exceptional regenerative capabilities, to analyze the pathology of IS and the subsequent recovery process. We induced photothrombosis in the telencephalon utilizing rose bengal and conducted a temporal investigation of changes in cerebral vascular function and learning ability. Our findings revealed that blood flow in young zebrafish was restored approximately 7 days post-IS induction (dpi), with brain function recuperating by 14 dpi. Furthermore, we observed an escalation in the expression of the neural stem marker gene at 3dpi, followed by an upregulation of the differentiated neuron marker at 7 and 14dpi. In the aged IS model, symptoms were exacerbated. While cerebral blood flow was restored in 7 days, similar to young zebrafish, the recovery of learning ability was protracted in aged fish. Moreover, an upregulation of the differentiated neuron marker seen in young fish was not observed in the aged model. Collectively, our analysis of the zebrafish IS model and its comparison with existing rodent models may lay the groundwork for novel IS treatment strategies. Furthermore, the zebrafish IS model may prove beneficial for analyzing the impact of aging on the pathology of IS and the recovery process.
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issn 1873-2747
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spelling doaj-art-8e8ef5d916234395aff4cf9760bb03772025-02-07T04:46:47ZengElsevierBrain Research Bulletin1873-27472025-02-01221111225Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathologyTakamasa Mizoguchi0Ayumi Maki1Yuno Nakase2Mayu Okita3Yuina Minami4Misa Fukunaga5Motoyuki Itoh6Graduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan; Research Institute of Disaster Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan; Health and Disease Omics Center, Chiba University, Chiba, Japan; Corresponding author at: Graduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of this condition, therapeutic options remain limited, with a pressing challenge being the development of treatments aimed at restoring neurological function. In this study, we leveraged zebrafish, renowned for their exceptional regenerative capabilities, to analyze the pathology of IS and the subsequent recovery process. We induced photothrombosis in the telencephalon utilizing rose bengal and conducted a temporal investigation of changes in cerebral vascular function and learning ability. Our findings revealed that blood flow in young zebrafish was restored approximately 7 days post-IS induction (dpi), with brain function recuperating by 14 dpi. Furthermore, we observed an escalation in the expression of the neural stem marker gene at 3dpi, followed by an upregulation of the differentiated neuron marker at 7 and 14dpi. In the aged IS model, symptoms were exacerbated. While cerebral blood flow was restored in 7 days, similar to young zebrafish, the recovery of learning ability was protracted in aged fish. Moreover, an upregulation of the differentiated neuron marker seen in young fish was not observed in the aged model. Collectively, our analysis of the zebrafish IS model and its comparison with existing rodent models may lay the groundwork for novel IS treatment strategies. Furthermore, the zebrafish IS model may prove beneficial for analyzing the impact of aging on the pathology of IS and the recovery process.http://www.sciencedirect.com/science/article/pii/S0361923025000371ZebrafishIschemic strokeAgingLearning abilityCerebral vascular function
spellingShingle Takamasa Mizoguchi
Ayumi Maki
Yuno Nakase
Mayu Okita
Yuina Minami
Misa Fukunaga
Motoyuki Itoh
Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
Brain Research Bulletin
Zebrafish
Ischemic stroke
Aging
Learning ability
Cerebral vascular function
title Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
title_full Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
title_fullStr Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
title_full_unstemmed Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
title_short Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology
title_sort neurological function is restored post ischemic stroke in zebrafish with aging exerting a deleterious effect on its pathology
topic Zebrafish
Ischemic stroke
Aging
Learning ability
Cerebral vascular function
url http://www.sciencedirect.com/science/article/pii/S0361923025000371
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