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Triiodothyronine Aggravates Global Cerebral Ischemia-Reperfusion Injury in Mice. | LitMetric

AI Article Synopsis

  • Thyroid hormones (THs) are crucial for brain function and low levels (hypothyroidism) may worsen injuries in stroke patients.
  • This study tested whether T, the active form of TH, could reduce neuronal damage in mice experiencing global cerebral ischemia (GCI).
  • Results showed that administering T actually increased DNA fragmentation and inflammatory responses in the brain, suggesting that high levels of T could worsen ischemic stroke effects during hypothyroidism treatment.

Article Abstract

Thyroid hormones (THs) have been suggested to play an important role in both physiological and pathological events in the central nervous system. Hypothyroidism, which is characterized by low levels of serum THs, has been associated with aggravation of ischemic neuronal injuries in stroke patients. We hypothesized that administration of T, the main active form of THs, may attenuate the ischemic neuronal injuries. In mice, global cerebral ischemia (GCI), which is induced by transient occlusion of the bilateral common carotid artery, causes neuronal injuries by inducing neuronal death and activating inflammatory responses after reperfusion in the hippocampus. In this study, we examined the effect of T administration on DNA fragmentation induced by neuronal death and the activation of inflammatory cells such as astrocytes and microglia in the hippocampus following GCI. The content of nucleosomes generated by DNA fragmentation in the hippocampus was increased by GCI and further increased by T administration. The protein expression levels of glial fibrillary acidic protein (GFAP), an astrocytic marker, and Ionized calcium binding adaptor protein 1 (Iba1), a microglial marker, in the hippocampus were also increased by GCI and further increased by T administration. The levels of T in both the serum and hippocampus were elevated by T administration. Our results indicate that T administration aggravates GCI-reperfusion injury in mice. There may be an increased risk of aggravation of ischemic stroke by the excessive elevation of T levels during the drug treatment of hypothyroidism.

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Source
http://dx.doi.org/10.1248/bpb.b21-00424DOI Listing

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