title: Hypothyroid state does not protect but delays neuronal death in the hippocampal CA1 region following transient cerebral ischemia: focus on oxidative stress and gliosis.
abstract: We investigated protective effects of hypothyroidism on delayed neuronal death, gliosis, lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) in the gerbil hippocampal CA1 region (CA1) after 5 min of transient cerebral ischemia. The hypothyroidism was induced by 0.025% methimazole treatment. Free triiodothyronine and thyroxine levels were markedly decreased in the hypothyroid group. Four days after ischemia/reperfusion, only a few NeuN-immunoreactive (+) neurons were detected in the CA1 of euthyroid-ischemia (eu-ischemia) group; however, at this time point, the number of NeuN(+) neurons was significantly higher in the hypothyroid-ischemia (hypo-ischemia) group than in the eu-ischemia group. At 5 days postischemia, NeuN(+) neurons were significantly decreased in the hypo-ischemia group: The number of NeuN(+) neurons in this group was similar to that in the eu-ischemia group. Activations of GFAP(+) astrocytes and Iba-1(+) microglia in the CA1 were higher in the eu-ischemia group 3 and 4 days after ischemia/reperfusion. At 5 days postischemia, the activations of both the glial cells in the CA1 were similar between the two groups. 4-Hydroxy-2-nonenal (HNE), a marker for lipid peroxidation, immunoreactivity in the eu-ischemia group was higher than in the hypo-ischemia group; at 5 days postischemia, the immunoreactivity was similar between the two groups. In contrast, SOD1 level was lower in the CA1 of the eu-ischemia group. These results suggest that hypothyroid state does not protect against delayed neuronal death but only delays the neuronal death in the hippocampal CA1 region after transient cerebral ischemia by reducing lipid peroxidation and increasing SOD1.
authors.affiliation: Department of Anatomy and Neurobiology and Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Il-Jun
authors.initials: IJ
authors.lastname: Kang
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D005911:Gliosis / Q000378:metabolism* / Q000473:pathology; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1