Alterations in the neural growth hormone axis following hypoxic-ischemic brain injury

Recently, there has been considerable interest in determining the role of t he growth hormone receptor (GHR) in the central nervous system (CNS). The a im 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) i mmunoreactivity to be rapidly upregulated following a severe unilateral HT injury. There was a biphasic increase with an initial rise occurring in blo od vessels within a few hours after injury followed by a secondary rise evi dent by 3 days post-hypoxia in microglia/macrophages, some of which are des tined to express insulin-like growth factor-I (IGF-I). There was also an in creased immunonactivity in reactive astrocytes, some of which were in the p rocess of dividing. Subsequently, we attempted to activate the endothelial GHR/BP which was found to be increased after injury by treating with 15 mu g g(-1) day(-1) s.c. bGH for 7 days. Circulating concentrations of IGF-I fe ll after injury and were restored with GH treatment (P = 0.001), whereas tr eatment of normal animals had no effect on serum IGF-I. Peripheral GH treat ment increased the cerebrospinal fluid (CSF) concentration of immunoreactiv e IGF-I in the injured rats (P = 0.017). GH treatment also reversed the sys temic catabolism caused by the injury but had no significant neuroprotectiv e effects. These results indicate that GH therapy can be used to reverse th e systemic catabolism that occurs after CNS injury. In addition, these data suggest a role for the neural GHR during the recovery from brain injury, b oth in terms of the induction of IGF-I and in terms of glial proliferation. (C) 1999 Elsevier Science B.V. All rights reserved.