Asphyxial brain injury--the role of the IGF system.
Transient neural injuries, such as asphyxia, can trigger considerable delayed neuronal death. Inappropriate induction of apoptosis is thought to play an important role in this process. Our studies have shown marked changes in the IGF system in the brain in response to these injuries with an induction of insulin growth factor (IGF)-1 and insulin growth factor binding protein (IGFBP)-2 and IGFBP-3 in glial cells in the region of injury. This suggests that the IGF-1 system may be an endogenous neuroprotective system. Earlier administration of IGF-1 - 2 h after injury reduced the phase of secondary neuronal loss suggesting that IGF-1 may well have therapeutic potential as a neuronal rescue agent. The action of IGF-1 appears to involve binding proteins, transport to the site of injury and the IGF-1 receptor and inhibition of apoptosis, but might also involve generation of GPE which itself appears to be neuroprotective. Together these results indicate considerable potential of these agents to treat stroke, perinatal asphyxia and other forms of acute brain injury.
Research Centre for Developmental Medicine and Biology, School of Medicine, University of Auckland, New Zealand. pd.gluckman@auckland.ac.nz
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PD
Gluckman
J
J
Guan
C
C
Williams
A
A
Scheepens
R
R
Zhang
L
L
Bennet
A
A
Gunn
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001237:Asphyxia / Q000503:physiopathology*; D006801:Humans; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D013002:Somatomedins / Q000502:physiology* / Q000627:therapeutic use
D018696:Neuroprotective Agents; D013002:Somatomedins