title: T3 replacement does not prevent excitotoxic cell death but reduces developmental neuronal apoptosis in newborn mice.
abstract: BACKGROUND
  Periventricular leukomalacia (PVL) is a major cause of neurological handicap in pre-term infants. At present, there are no effective or causal therapies available. Thyroid hormones play an essential role in brain development and are reported to be decreased in pre-terms and following brain injury in adults.
  
  
  OBJECTIVE
  Excitotoxic brain damage of newborn mice decreases thyroid hormone concentrations. Exogenous T3 administration restores thyroid hormone levels and reduces perinatal brain damage in an animal model of PVL.
  
  
  METHODS
  To create white and gray matter (WM/GM) lesion mimicking several key aspects of PVL, we injected ibotenic acid (Ibo), a glutamate analog, into the right hemisphere (intracranially (i.c.)) of 5-day-old mice. T3 (10 microg/kg body weight (bw)) was injected intraperitoneally (i.p.) 1 h or repeatedly 1/24/48/72/96 h post-insult. We determined lesion size, number of apoptotic cells in WM/GM and serum T3/T4 concentration at 24 and 120 h after injury. Serum T3/T4 concentration was also determined before and 1 and 2h after T3 administration.
  
  
  RESULTS
  Excitotoxic brain damage did not alter serum T3/T4 concentrations within 120 h of injury. Serum T3 levels were distinctly elevated within 1 h of T3 injection; however, this elevation was relatively short-lived (half-life estimated to be less than 12 h). Neither single nor repetitive T3 treatment regimen reduced excitotoxic lesion size, but it did reduce apoptosis.
  
  
  CONCLUSIONS
  T3 replacement does not prevent excitotoxic cell death, but it does reduce developmental neuronal apoptosis, which could participate to the beneficial neuropsychological effects of hormone therapy. Further study is therefore warranted.
authors.affiliation: Department of Paediatrics IV, Neonatology, Neuropediatrics and Metabolic Diseases, Medical University Innsbruck, Anichstrasse 35, Innsbruck, Austria.
authors.forename: Gergely
authors.initials: G
authors.lastname: Sárközy
authors.forename: Elke
authors.initials: E
authors.lastname: Griesmaier
authors.forename: Xiangying
authors.initials: X
authors.lastname: He
authors.forename: Klaus
authors.initials: K
authors.lastname: Kapelari
authors.forename: Martina
authors.initials: M
authors.lastname: Urbanek
authors.forename: Georg
authors.initials: G
authors.lastname: Simbruner
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Matthias
authors.initials: M
authors.lastname: Keller
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality; D007051:Ibotenic Acid / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D013997:Time Factors; D014284:Triiodothyronine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D018690:Excitatory Amino Acid Agonists; C425161:triiodothyropropionine; D014284:Triiodothyronine; D007051:Ibotenic Acid; D053148:Caspase 3