Protective effect of growth hormone on neuronal apoptosis after hypoxia-ischemia in the neonatal rat brain.
Recent studies have shown that growth hormone (GH) can reduce neuronal loss after hypoxic-ischemic injury (HI) in neonatal and juvenile rat brains. Here, we investigated whether GH exerts its neuroprotective role through an anti-apoptotic effect in neonatal rat brains damaged by severe HI. Gross and histological observations showed that the extent of brain damage was found to be reduced in GH-treated brain at E7 after injury. In a terminal transferase-mediated dUTP nick-end-labeling (TUNEL) study, TUNEL-positive apoptotic cells were localized only at the damaged region in animals treated with saline, which was confirmed by an electron microscopy. In an immunohistochemical study with anti-bcl-2, -bax, -bad, -neuronal nitric oxide synthase (nNOS), -inducible NOS (iNOS) and -endothelial NOS (eNOS) antibodies, we observed that bax, bad, iNOS and eNOS were elevated in the saline-treated group. This study thus suggests that the protective role of GH against HI injury is mediated thorough an anti-apoptotic effect, which offers the possibility of a GH application for the treatment of neonatal HI encephalopathy.
Shin
Dong Hoon
DH
Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
Lee
Eunju
E
Kim
Jong-Wan
JW
Kwon
Bum-Sun
BS
Jung
Mi Kyung
MK
Jee
Youn Hee
YH
Kim
Jaehyup
J
Bae
Su-ryeon
SR
Chang
Young Pyo
YP
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
C494821:Bad protein, rat; C494828:Bax protein, rat; D002352:Carrier Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D013006:Growth Hormone; D019001:Nitric Oxide Synthase