Post-ischaemic thyroid hormone treatment in a rat model of acute stroke

Tiziana Genovese, Daniela Impellizzeri, Akbar Ahmad, Carolin Cornelius, Michela Campolo, Salvatore Cuzzocrea, Emanuela Esposito

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Stroke is a devastating brain injury that is a leading cause of adult disability with limited treatment options. We examined the effects of prohormone thyroxine (T4) and the underlying mechanisms in the post-ischaemic rat brain after transient focal cerebral ischemia-induced brain injury. Ischaemic injury was induced for 2 h by middle cerebral artery occlusion (MCAo) followed by 24-h reperfusion. T4 (1.1 μg/100 g BW) was administered by intraperitoneally injection twice, at 1 after the onset of ischemia and 6 h after reperfusion. Cerebral infarct area and infarct volume were measured 24 h after MCAo. Furthermore, the mechanism of neuroprotective effect of T4 was investigated with a focus on inflammatory cells, neurotrophins, and transcriptional factors. T4 significantly reduced cerebral infarction, which were accompanied by decreased expression of proapotptic Bax and increased antiapoaptotic Bcl-2 protein. T4 suppressed the activation of astrocytes and microglia, increased the expression of neurotrophic factors (BDNF, GDNF), and altered inflammatory-related prooxidative enzymes (iNOS and COX-2) in ischaemic brain. Moreover, T4 downregulated the phosphorylation of p38 and prevented injury-induced increase of PKCδ. These results revealed that T4 has a promising therapeutic effect in ischaemic stroke treatment protecting the brain from I/R injury, probably by its anti-apoptotic, and anti-inflammatory mechanism.

Original languageEnglish (US)
Pages (from-to)92-102
Number of pages11
JournalBrain Research
Volume1513
DOIs
StatePublished - Jun 4 2013

Keywords

  • Cerebral ischaemia
  • Neuroprotection
  • Thyroid hormone
  • l-Thyroxine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Genovese, T., Impellizzeri, D., Ahmad, A., Cornelius, C., Campolo, M., Cuzzocrea, S., & Esposito, E. (2013). Post-ischaemic thyroid hormone treatment in a rat model of acute stroke. Brain Research, 1513, 92-102. https://doi.org/10.1016/j.brainres.2013.03.001