title: The effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate in different regions following hypoxic-ischemic brain injury in adult rats.
abstract: Insulin-like growth factor-1 has pleiotropic effects in the central nervous system and can act both as a survival and a differentiation factor. Insulin-like growth factor-1 can be proteolytically cleaved into des-N-(1-3)-insulin-like growth factor-1 and a N-terminal tripeptide fragment, glycine-proline-glutamate. Both insulin-like growth factor-1 and des-N-(1-3)-insulin-like growth factor-1 can improve neuronal survival after hypoxic-ischemic brain injury in vivo. The present study investigates the effects of glycine-proline-glutamate on different brain regions and neuronal populations after hypoxic-ischemic injury. Unilateral hypoxic-ischemic injury was induced in adult rats. Glycine-proline-glutamate (3 microg) was administered centrally 2 h after the injury and the extent of brain damage determined five days later. In a separate trial immunohistochemical techniques were used to determine the effects of glycine-proline-glutamate on specific populations of neurons in the striatum after the injury. Compared to the vehicle treatment, glycine-proline-glutamate (n=19) treatment reduced the extent of cortical damage and neuronal loss in the CA1-2 subregions of the hippocampus (P<0.05). In the striatum, there was a trend towards a reduction in neuronal loss after glycine-proline-glutamate treatment (P=0.053) compared to the vehicle (n=21)-treated animals. In a separate study, glycine-proline-glutamate (n=8) treatment prevented the loss of choline acetyltransferase (P<0.05), glutamate acid decarboxylase (P<0.05) and somatostatin (P<0.05) containing neurons in the ipsilateral striatum following hypoxic-ischemic brain injury and also increased the numbers of neuronal nitric oxide synthase (P<0.05) containing neurons in the contralateral side. These studies suggest that in addition to neuroprotective effects, glycine-proline-glutamate can influence neuronal activity after hypoxic-ischemic injury.
authors: Research Centre for Developmental Medicine and Biology, University of Auckland, New Zealand.
authors: J
authors: J
authors: Guan
authors: H J
authors: HJ
authors: Waldvogel
authors: R L
authors: RL
authors: Faull
authors: P D
authors: PD
authors: Gluckman
authors: C E
authors: CE
authors: Williams
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003342:Corpus Striatum / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D005968:Glutamate Decarboxylase / Q000032:analysis; D006624:Hippocampus / Q000473:pathology*; D002534:Hypoxia, Brain / Q000188:drug therapy*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D013004:Somatostatin / Q000032:analysis
chemical_list: D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C062053:glycyl-prolyl-glutamic acid