Possible protective role of growth hormone in hypoxia-ischemia in neonatal rats

Perinatal asphyxia still constitutes a clinical hazard associated with considerable neurologic morbidity. Several growth factors, including insulin-like growth factor-I (IGF-I), have been reported to have a neuroprotective effect in experimental models of hypoxic ischemia (HI). In the present study, we have applied solution hybridization for quantification of the time course for mRNA expression of IGF-I, IGF-I receptor, and growth hormone (GK) receptor after HI in 7-d-old rats. There was a significant increase in IGF-I mRNA in the damaged hemisphere 72 h (1.19 +/- 0.28vs 0.48 +/- 0.02 amol/mu g DNA, p < 0.05) and 14 d (0.61 +/- 0.18 vs 0.19 +/- 0.05 amol/mu g DNA, p < 0.05) after HI. In the contralateral hemisphere, both IGF-I and GH receptor mRNA had increased by 14 d after the insult (0.36 +/- 0.042 vs 0.13 +/- 0.011, p < 0.05, and 0.31 +/- 0.013 vs 0.11 +/- 0.004 amol/mu g DNA, p < 0.001, respectively). There were no changes in IGF-I receptor mRNA throughout the study period. We have also evaluated the neuroprotective effect of GH after HI in neonatal rats. GH administered s.c. after HI in daily doses of 50 and 100 mg/kg provided a moderate neuroprotection of 20%. These results suggest a role for the GH/IGF-I axis in the neurochemical process leading to HI brain injury.