title: Treatment in animal models.
abstract: It is now well established that neurons and other cell types may die many hours or even days after hypoxic-ischemic injury due to activation of programmed cell death (apoptotic) pathways. The potent anti-apoptotic factor 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 endogenous brain recovery. Exogenous administration of IGF-1 within a few hours after brain injury has now been shown to be protective in both grey and white matter, and leads to improved long-term neurological function. The limited window of opportunity for treatment with IGF-1 can be extended by spontaneous mild post-hypoxic hypothermia, probably due to delayed evolution of apoptotic processes. The efficacy of IGF-1 is specific to particular cellular phenotypes and brain regions, and its neuroprotective effects are mediated by IGF-1 receptors and binding proteins. Intriguingly its naturally cleaved N-terminal tripeptide (glycine-proline-glutamate, GPE) has been demonstrated to be neuroprotective after both central and peripheral administration. Peripheral administration of GPE also prevents the loss of dopamine neurons and improves long-term functional recovery following 6-OHDA lesion. However, GPE is unlikely to contribute significantly to the direct effects of IGF-1.
authors.affiliation: The Liggins Institute, Faculty of Medicine and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.forename: L
authors.initials: L
authors.lastname: Bennet
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: A J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I