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Triiodothyronine treatment in mice improves stroke outcome and reduces blood-brain barrier damage

Ullrich, Daniel ; Führer, Dagmar ; Heuer, Heike ; Mayerl, Steffen ; Haupeltshofer, Steffen LU ; Schmitt, Linda-Isabell ; Leo, Markus ; Szepanowski, Rebecca D ; Hagenacker, Tim and Schwaninger, Markus , et al. (2025) In European Thyroid Journal 14(1).
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Triiodothyronine/therapeutic use, Blood-Brain Barrier/drug effects, Mice, Male, Stroke/drug therapy, Infarction, Middle Cerebral Artery/drug therapy, Mice, Inbred C57BL, Disease Models, Animal, Neuroprotective Agents/therapeutic use, Aquaporin 4/metabolism
in
European Thyroid Journal
volume
14
issue
1
article number
e240143
publisher
BioScientifica
external identifiers
  • pmid:39841728
  • scopus:86000349013
ISSN
2235-0640
DOI
10.1530/ETJ-24-0143
language
English
LU publication?
no
id
7dcae9c0-fdf3-4a41-8d22-c10adad4b977
date added to LUP
2026-01-20 09:57:16
date last changed
2026-01-21 04:02:05
@article{7dcae9c0-fdf3-4a41-8d22-c10adad4b977,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &lt; 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 &gt; 0.999). The protective effect of acute T3 treatment persisted for 72 h post-tMCAO (P &lt; 0.01) and accelerated the recovery of motor function by day 3 (P &lt; 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.</p><p>CONCLUSION: Our findings suggest that T3 may be a promising intervention for ischemic stroke in the acute phase.</p>}},
  author       = {{Ullrich, Daniel and Führer, Dagmar and Heuer, Heike and Mayerl, Steffen and Haupeltshofer, Steffen and Schmitt, Linda-Isabell and Leo, Markus and Szepanowski, Rebecca D and Hagenacker, Tim and Schwaninger, Markus and Kleinschnitz, Christoph and Langhauser, Friederike}},
  issn         = {{2235-0640}},
  keywords     = {{Animals; Triiodothyronine/therapeutic use; Blood-Brain Barrier/drug effects; Mice; Male; Stroke/drug therapy; Infarction, Middle Cerebral Artery/drug therapy; Mice, Inbred C57BL; Disease Models, Animal; Neuroprotective Agents/therapeutic use; Aquaporin 4/metabolism}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{1}},
  publisher    = {{BioScientifica}},
  series       = {{European Thyroid Journal}},
  title        = {{Triiodothyronine treatment in mice improves stroke outcome and reduces blood-brain barrier damage}},
  url          = {{http://dx.doi.org/10.1530/ETJ-24-0143}},
  doi          = {{10.1530/ETJ-24-0143}},
  volume       = {{14}},
  year         = {{2025}},
}