Insulin-like growth factor-1 and post-ischemic brain injury.
Insulin-like growth factor-1 (IGF-1) is a naturally occurring neurotrophic factor that plays an important role in promoting cell proliferation and differentiation during normal brain development and maturation. The present review examines recent evidence that endogenous IGF-1 also plays a significant role in recovery from insults such as hypoxia-ischemia and that giving additional exogenous IGF-1 can actively ameliorate damage. It is now well established that neurons and other cell types die many hours or even days after initial injury due to activation of programmed cell death pathways. IGF-1 and its binding proteins and receptors are intensely induced within damaged brain regions following brain injury, suggesting a possible a role for IGF-1 in brain recovery. Exogenous administration of IGF-1 within a few hours after brain injury is now known to be protective in both gray and white matter and leads to improved somatic function. In contrast, pre-treatment is ineffective, likely reflecting limited intracerebral penetration of IGF-1 into the uninjured brain. The neuroprotective effects of IGF-1 are mediated by IGF-1 receptors and its binding proteins and are specific to particular cellular phenotypes and brain regions. The window of opportunity for treatment with IGF-1 is limited to a few hours after normothermic brain injury, reflecting its specific actions on early, intracellular events in the apoptotic cascade. However, injury-associated mild post-hypoxic hypothermia, which delays the development of cell death, can shift and dramatically extend the window of opportunity for delayed treatment with IGF-1. Such a combined approach is likely to be essential for any clinical treatment.
Faculty of Medicine and Health Sciences, The Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand. j.guan@auckland.ac.nz
J
J
Guan
L
L
Bennet
P D
PD
Gluckman
A J
AJ
Gunn
D000818:Animals; D017209:Apoptosis; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013997:Time Factors
D018969:Insulin-Like Growth Factor Binding Proteins; D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1