Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage
Objective: Thyroid hormones control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3′,5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage...
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Bioscientifica
2025-02-01
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| Series: | European Thyroid Journal |
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| Online Access: | https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0143.xml |
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| author | Daniel Ullrich Dagmar Führer Heike Heuer Steffen Mayerl Steffen Haupeltshofer Linda-Isabell Schmitt Markus Leo Rebecca D Szepanowski Tim Hagenacker Markus Schwaninger Christoph Kleinschnitz Friederike Langhauser |
| author_facet | Daniel Ullrich Dagmar Führer Heike Heuer Steffen Mayerl Steffen Haupeltshofer Linda-Isabell Schmitt Markus Leo Rebecca D Szepanowski Tim Hagenacker Markus Schwaninger Christoph Kleinschnitz Friederike Langhauser |
| author_sort | Daniel Ullrich |
| collection | DOAJ |
| description | Objective: Thyroid hormones control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3′,5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. Methods: Stroke was induced in mice by transient middle cerebral artery occlusion (tMCAO), and T3 was administered at different doses and time points before and after stroke. Results: We demonstrated a dose-dependent protective effect of T3 reducing infarct volumes with an optimal T3 dosage of 25 μg/kg. In addition, we observed a time-dependent effectiveness that was most profound when T3 was administered 1 h after tMCAO (P < 0.001), with a gradual reduction in efficacy at 4.5 h (P = 0.066), and no reduction in infarct volumes when T3 was injected with an 8-h delay (P > 0.999). The protective effect of acute T3 treatment persisted for 72 h post-tMCAO (P < 0.01) and accelerated the recovery of motor function by day 3 (P < 0.05). In-depth investigations further revealed reduced cerebral edema and diminished blood–brain barrier leakage, indicated by reduced extravasation of Evans blue and diminished aquaporin-4 expression. Conclusion: Our findings suggest that T3 may be a promising intervention for ischemic stroke in the acute phase. |
| format | Article |
| id | doaj-art-a6a0b6ddf497428c843358ffd340a4a0 |
| institution | Kabale University |
| issn | 2235-0802 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | European Thyroid Journal |
| spelling | doaj-art-a6a0b6ddf497428c843358ffd340a4a02025-02-09T12:03:46ZengBioscientificaEuropean Thyroid Journal2235-08022025-02-0114110.1530/ETJ-24-01431Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damageDaniel Ullrich0Dagmar Führer1Heike Heuer2Steffen Mayerl3Steffen Haupeltshofer4Linda-Isabell Schmitt5Markus Leo6Rebecca D Szepanowski7Tim Hagenacker8Markus Schwaninger9Christoph Kleinschnitz10Friederike Langhauser11Department of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyDepartment of Neurology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyObjective: Thyroid hormones control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3′,5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. Methods: Stroke was induced in mice by transient middle cerebral artery occlusion (tMCAO), and T3 was administered at different doses and time points before and after stroke. Results: We demonstrated a dose-dependent protective effect of T3 reducing infarct volumes with an optimal T3 dosage of 25 μg/kg. In addition, we observed a time-dependent effectiveness that was most profound when T3 was administered 1 h after tMCAO (P < 0.001), with a gradual reduction in efficacy at 4.5 h (P = 0.066), and no reduction in infarct volumes when T3 was injected with an 8-h delay (P > 0.999). The protective effect of acute T3 treatment persisted for 72 h post-tMCAO (P < 0.01) and accelerated the recovery of motor function by day 3 (P < 0.05). In-depth investigations further revealed reduced cerebral edema and diminished blood–brain barrier leakage, indicated by reduced extravasation of Evans blue and diminished aquaporin-4 expression. Conclusion: Our findings suggest that T3 may be a promising intervention for ischemic stroke in the acute phase.https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0143.xmlblood–brain barrierischemic stroketriiodothyroninet3tmcao |
| spellingShingle | Daniel Ullrich Dagmar Führer Heike Heuer Steffen Mayerl Steffen Haupeltshofer Linda-Isabell Schmitt Markus Leo Rebecca D Szepanowski Tim Hagenacker Markus Schwaninger Christoph Kleinschnitz Friederike Langhauser Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage European Thyroid Journal blood–brain barrier ischemic stroke triiodothyronine t3 tmcao |
| title | Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage |
| title_full | Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage |
| title_fullStr | Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage |
| title_full_unstemmed | Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage |
| title_short | Triiodothyronine treatment in mice improves stroke outcome and reduces blood–brain barrier damage |
| title_sort | triiodothyronine treatment in mice improves stroke outcome and reduces blood brain barrier damage |
| topic | blood–brain barrier ischemic stroke triiodothyronine t3 tmcao |
| url | https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0143.xml |
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