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

Insulin-like growth factor-1 has pleiotropic effects in the central nervous system and can act both as a survival and a differentiation factor. Insuli n-like growth factor-1 can be proteolytically cleaved into des-N-(1-3)-insu lin-like growth factor-1 and a N-terminal tripeptide fragment, glycine-prol ine-glutamate. Both insulin-like growth factor-1 and des-N-(1-3)-insulin-li ke growth factor-1 can improve neuronal survival after hypoxic-ischemic bra in injury in vivo. The present study investigates the effects of glycine-pr oline-glutamate on different brain regions and neuronal populations after h ypoxic-ischemic injury. Unilateral hypoxic-ischemic injury was induced in a dult rats. Glycine-proline-glutamate (3 mu g) was administered centrally 2 h after the injury and the extent of brain damage determined five days late r. In a separate trial immunohistochemical techniques were used to determin e the effects of glycine-proline-glutamate on specific populations of neuro ns in the striatum after the injury: Compared to the vehicle treatment, gly cine-proline-glutamate (n=19) treatment reduced the extent of cortical dama ge and neuronal loss in the CA1-2 subregions of the hippocampus (P<0.05). I n the striatum, there was a trend towards a reduction in neuronal loss afte r glycine-proline-glutamate treatment (P=0.053) compared to the vehicle (n= 21)-treated animals. In a separate study, glycine-proline-glutamate (n=8) t reatment prevented the loss of choline acetyltransferase (P<0.05), glutamat e acid decarboxylase (P<0.05) and somatostatin (P<0.05) containing neurons in the ipsilateral striatum following hypoxic-ischemic brain injury and als o increased the numbers of neuronal nitric oxide synthase (P<0.05) containi ng neurons in the contralateral side. These studies suggest that in addition to neuroprotective effects, glycine- proline-glutamate can influence neuronal activity after hypoxic-ischemic in jury. (C) 1999 IBRO. Published by Elsevier Science Ltd.