Alterations in the neural growth hormone axis following hypoxic-ischemic brain injury.
Recently, there has been considerable interest in determining the role of the growth hormone receptor (GHR) in the central nervous system (CNS). The aim of this study was to investigate the role of circulating growth hormone (GH) and the neural GHR after hypoxic-ischemic (HI) brain injury in the 21-day old rat. We observed growth hormone receptor/binding protein (GHR/BP) immunoreactivity to be rapidly upregulated following a severe unilateral HI injury. There was a biphasic increase with an initial rise occurring in blood vessels within a few hours after injury followed by a secondary rise evident by 3 days post-hypoxia in microglia/macrophages, some of which are destined to express insulin-like growth factor-I (IGF-I). There was also an increased immunoreactivity in reactive astrocytes, some of which were in the process of dividing. Subsequently, we attempted to activate the endothelial GHR/BP which was found to be increased after injury by treating with 15 microgram g-1 day-1 s.c. bGH for 7 days. Circulating concentrations of IGF-I fell after injury and were restored with GH treatment (P=0.001), whereas treatment of normal animals had no effect on serum IGF-I. Peripheral GH treatment increased the cerebrospinal fluid (CSF) concentration of immunoreactive IGF-I in the injured rats (P=0.017). GH treatment also reversed the systemic catabolism caused by the injury but had no significant neuroprotective effects. These results indicate that GH therapy can be used to reverse the systemic catabolism that occurs after CNS injury. In addition, these data suggest a role for the neural GHR during the recovery from brain injury, both in terms of the induction of IGF-I and in terms of glial proliferation.
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D005260:Female; D013006:Growth Hormone / Q000502:physiology*; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009336:Necrosis; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar