Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor

Pi Lien Hung, Chao Ching Huang, Hsiu Mei Huang, Dom Gene Tu, Ying Chao Chang

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)

摘要

BACKGROUND AND PURPOSE-: Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. METHODS-: Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. RESULTS-: On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. CONCLUSIONS-: T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

原文英語
頁(從 - 到)2275-2283
頁數9
期刊Stroke
44
發行號8
DOIs
出版狀態已發佈 - 8月 2013
對外發佈

ASJC Scopus subject areas

  • 心臟病學與心血管醫學
  • 神經病學(臨床)
  • 高級和專業護理

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