Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and alters Akt/glycogen synthase kinase-3beta phosphorylation

• Hexarelin (HEX) is a peptide GH secretagogue with a potent ability to stimulate GH secretion and recently reported cardioprotective actions. However, its effects in the brain are largely unknown, and the aim of the present study was to examine the potential protective effect of HEX on the central nervous system after injury, as well as on caspase-3, Akt, and extracellular signal-regulated protein kinase (ERK) signaling cascades in a rat model of neonatal hypoxia-ischemia. Hypoxic-ischemic insult was induced by unilateral carotid ligation and hypoxic exposure (7.7% oxygen), and HEX treatment was administered intracerebroventricularly, directly after the insult. Brain damage was quantified at four coronal levels and by regional neuropathological scoring. Brain damage was reduced by 39% in the treatment group, compared with vehicle group, and injury was significantly reduced in the cerebral cortex, hippocampus, and thalamus but not in the striatum. The cerebroprotective effect was accompanied by a significant reduction of caspase-3 activity and an increased phosphorylation of Akt and glycogen synthase kinase-3beta, whereas ERK was unaffected. In conclusion, we demonstrate for the first time that HEX is neuroprotective in the neonatal setting in vivo and that increased Akt signaling is associated with downstream attenuation of glycogen synthase kinase-3beta activity and caspase-dependent cell death.

Nyckelord

Animals

Animals

Newborn

Brain Ischemia/metabolism/*pathology

Caspase 3

Caspases/antagonists & inhibitors

Female

Glycogen Synthase Kinase 3/*metabolism

Growth Hormone/metabolism

Hypoxia

Brain/metabolism/*pathology

Immunohistochemistry

Insulin-Like Growth Factor I/metabolism

Male

Neuroprotective Agents/*pharmacology

Oligopeptides/*pharmacology

Phosphorylation/drug effects

Rats

Rats

Wistar

Receptor

IGF Type 1/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)