title: Post-ischaemic thyroid hormone treatment in a rat model of acute stroke.
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 2h by middle cerebral artery occlusion (MCAo) followed by 24-h reperfusion. T4 (1.1μg/100g BW) was administered by intraperitoneally injection twice, at 1 after the onset of ischemia and 6h after reperfusion. Cerebral infarct area and infarct volume were measured 24h 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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.forename: Carolin
authors.initials: C
authors.lastname: Cornelius
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009460:Neurologic Examination; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: C100745:Aif1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008840:Microfilament Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013974:Thyroxine