Delayed IGF-1 treatment reduced long-term hypoxia-ischemia-induced brain damage and improved behavior recovery of immature rats

Jin Zhong, Limin Zhao, Yansheng Du, Gang Wei, Wei Guo Yao, Wei Hua Lee

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute newborn mortality and chronic disability. Despite our increasing understanding of the mechanisms of neuronal injury, an effective clinical therapy has yet to be established to mitigate brain damage and improve the prognosis and well-being of these newborn patients. Insulin-like growth factor 1 (IGF-1) is a well-known neurotrophic factor, essential for the survival and functional maturation of immature neurons. This study demonstrated that subcutaneous administration of IGF-1 at 24 and 48 hours of recovery significantly reduced hypoxia-ischemia-induced injury to immature rat brains and improved long-term memory and cognitive behavior. IGF-1's therapeutic effects likely involve its ability to prevent delayed apoptosis, as we demonstrated in primary cortical neuronal cultures under oxygen and glucose deprivation. IGF-1's neuroprotective effects parallel the activities of phosphatidylinositol-3/Akt and its downstream signaling pathway, suggesting a potential mechanistic link. Overall, evidence from this investigation strongly supports IGF-1's potential therapeutic use in the treatment of hypoxic-ischemic encephalopathy in newborn patients.

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalNeurological Research
Volume31
Issue number5
DOIs
StatePublished - Jun 1 2009

    Fingerprint

Keywords

  • Apoptosis
  • Brain
  • Hypoxic-ischemic encephalopathy
  • Insulin like growth factor-1
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this