Abstract
Background: PVL is a major cause of neurodevelopmental delay and lifelong handicaps in preterm infants. Until now effective or causal therapy is not available. Thyroid hormons play essential role in brain maturation and are known to be decreased after brain injuries in adults. Substitution of T3, the metabolically most active thyroid hormone, thus might mitigate brain injuries.
Hypotheses: Excitotoxic brain damage of newborn mice decreases thyroid hormon levels. Exogenous T3 administration restores thyroid hormon level and is neuroprotective.
Methods: We used a newborn mice model of PVL. We injected ibotenic acid (glutamate-analogue) into one hemisphere of five day old mice to create white and grey matter lesion. 3,3‘,5-Triiodo-L-thyronine (100μg) was injected intraperitoneally in a randomized fashion once at 1 hr or repeatedly at 1/24/48/72/96 hrs after injury. Animals were randomized into 4 groups: 1. hormon level (T3+T4) measurement without intervention 2. ibotenic acid intracranial 3. ibotenic acid intracranial + T3 once intraperitoneal 4. ibotenic acid + T3 repeatedly intraperitoneal. Study time-endpoints were at the time of setting the lesion and 24/120 hrs later. Study endpoints were histological assessement of the lesion size (mean length of rostro-caudal axis of the lesion) and/or hormonlevel measurement.
Results: Serum T3 levels decreased significantly while T4 significantly increased with advanced postnatal age. Induced brain damage did not influence serum T3/T4 levels 24/120 hrs after setting the lesion. There was no discernible change in serum T3/T4 levels 24/120 hrs after injection of T3. Neither a single nor repeated injection of T3 had significant effect on lesion size in grey/white matter assessed 24/120 hours after setting the lesion.
Summary: Excitotoxic brain damage does not significantly change serum T3 and T4 levels in newborn mice. Supplementary T3 injection at the dosage regimen used was neither neuroprotectiv nor increased regenerative capacities after excititoxic brain damage in newborn mice.
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Sárközy, G., Simbruner, G., Xiagying, H. et al. 325 Effect of Triiodothyronine (T3) on Excitotoxic Brain Damage of Newborn Mice. Pediatr Res 58, 410 (2005). https://doi.org/10.1203/00006450-200508000-00354
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DOI: https://doi.org/10.1203/00006450-200508000-00354