Bimodal upregulation of glial cell line-derived neurotrophic factor (GDNF) in the neonatal rat brain following ischemic/hypoxic injury.
In order to delineate the spatial and temporal patterns of glial cell line-derived neurotrophic factor (GDNF) expression following ischemic/hypoxic injury in immature and neonatal brain, GDNF protein levels and immunocytochemistry were studied in rats subjected to a modified Levine procedure. Significant upregulation of GDNF protein occurred in a bimodal fashion in the damaged left cerebral cortex and hippocampus, while the levels in the right cerebral hemisphere of both control and ischemic groups remained relatively unchanged. Immunocytochemical studies indicated that the early rise in GDNF levels was most likely to be related to enhanced neuronal release of GDNF. The second rise was probably related to progressive astrogliosis that occurred in response to injury. In contrast to the lack of GDNF expression among astrocytes in normal mature brains, reactive astrocytes in the neonate appear to possess a ready capacity to express GDNF. Spatial and temporal changes in the pattern of GDNF expression following injury, as determined in this study may provide insight into the functions of GDNF in vivo and into possible therapeutic approaches toward prevention of damage or rescue of neurons following brain injury.
Ikeda
Tomoaki
T
Department of Obstetrics and Gynecology, Miyazaki Medical College, 5200 Kihara, Kiyotake-Cho, Japan. tikeda@postl.miyazaki-med.ac.jp
Koo
Heasoo
H
Xia
Yi X
YX
Ikenoue
Tsuyomu
T
Choi
Ben H
BH
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006624:Hippocampus / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D015854:Up-Regulation
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors