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Related Concept Videos

Synthesis and Regulation of Thyroid Hormones01:20

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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Thyroid Hormone T4 Alleviates Traumatic Brain Injury by Enhancing Blood-Brain Barrier Integrity.

Mayuri Khandelwal1, Zhe Ying1, Fernando Gomez-Pinilla1,2

  • 1Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA.

International Journal of Molecular Sciences
|October 16, 2025
PubMed
Summary

Thyroid hormone (T4) therapy can protect the brain after traumatic brain injury (TBI). T4 treatment reduces blood-brain barrier (BBB) damage and improves cognitive function, offering a potential therapeutic strategy for TBI recovery.

Keywords:
blood–brain barriercognitionthyroid hormonetraumatic brain injury

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Vascular Biology

Background:

  • Traumatic brain injury (TBI) compromises blood-brain barrier (BBB) integrity, leading to neuronal loss and cognitive deficits.
  • Disruption of the BBB involves increased permeability, edema, and inflammation, exacerbating TBI-related damage.

Purpose of the Study:

  • To investigate the therapeutic efficacy of thyroid hormone (T4) in mitigating BBB dysfunction following TBI.
  • To evaluate T4's impact on cellular components, molecular markers, and cognitive outcomes post-TBI.

Main Methods:

  • Administration of T4 via intraperitoneal injection following moderate fluid percussion injury in a TBI model.
  • Assessment of BBB integrity markers, including pericyte and endothelial cell levels, AQP-4 and ZO-1 expression, and MMP-9 and TLR-4 activity.
  • Evaluation of astrocyte function, DHA levels, mitochondrial biogenesis, and spatial learning and memory retention.

Main Results:

  • T4 treatment restored pericyte and endothelial cell levels, downregulated AQP-4, and increased ZO-1, indicating BBB repair.
  • T4 counteracted TBI-induced MMP-9 and TLR-4 upregulation, significantly reducing BBB permeability and inflammation.
  • T4 enhanced A2 astrocyte activity, increased DHA levels, stimulated mitochondrial biogenesis, and improved cognitive performance in spatial learning and memory tasks.

Conclusions:

  • Thyroid hormone (T4) demonstrates significant neuroprotective potential by preserving BBB integrity and reducing vascular leakage and inflammation after TBI.
  • T4 treatment offers a promising therapeutic avenue for improving cognitive function and mitigating long-term consequences associated with traumatic brain injury.