Grafting of glial cell line-derived neurotrophic factor secreting cells for hypoxic-ischemic encephalopathy in neonatal rats.
OBJECTIVE
It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system.


METHODS
Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined.


RESULTS
The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group.


CONCLUSIONS
Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult.
Katsuragi
Shinji
S
Department of Obstetrics and Gynecology, Miyazaki Medical College, Kiyotake-Cho, Miyazaki, Japan. skatsura12@yahoo.co.jp
Ikeda
Tomoaki
T
Date
Isao
I
Shingo
Tetsuro
T
Yasuhara
Takao
T
Ikenoue
Tsuyomu
T
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D017690:Cell Transplantation; D006224:Cricetinae; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000628:therapy*; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents