Novel Mechanisms of Neonatal Hypoxic-Ischemic Brain Injury and Repair

  • Lee, Wei-Hua, (PI)

Project: Research project

Description

Hypoxia-ischemia encephalopathy (HIE) remains a leading cause of severe brain damage that occurs in 0.1-0.2% of term or near-term infants, among whom approximately 20% die and up to 40% of the survivors often suffer devastating disabilities. To date, no effective clinical treatment is available to mitigate brain damage and improve the brain functional development of these children. Insulinlike growth factor I (IGF-I) is a pleiotrophic factor essential for the development of the mammalian nervous system. IGF-I reduced brain damage and improved the survival of hypoxic-ischemic rats and fetal sheep. Recently, we found that exogenous IGF-I was more effective in reducing hypoxic-ischemic brain injury and in improving functional behavior development,13 if given after 24 hours of recovery. We hypothesize that, in the delayed phase of hypoxia-ischemia recovery, IGF-I treatment will promote brain repair by (1) reducing delayed neuronal apoptosis;and (2) stimulating neuro- and oligodendrogenesis and revascularization. We will examine this novel hypothesis using complementary in vitro and in vivo models of hypoxia-ischemia. Aim 1 will characterize the mechanisms by which IGF-I prevents or reduces delayed neuronal apoptosis following hypoxia-ischemia. Aim 2 will investigate if and how IGF-I stimulates revascularization and neuro-/oligodendrogenesis following neonatal hypoxiaischemia. Results of this investigation will provide crucial information towards establishing an effective therapy for newborn patients suffering from hypoxicischemic encepholapathy.
StatusFinished
Effective start/end date9/30/098/31/12

Funding

  • National Institutes of Health: $385,000.00
  • National Institutes of Health: $364,480.00

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Brain Injuries
Intercellular Signaling Peptides and Proteins
Ischemia
Brain
Apoptosis
Brain Diseases
Child Development
Nervous System
Survivors
Sheep
Therapeutics
Newborn Infant
Hypoxia

Keywords

  • Medicine(all)