Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats

Shinji Katsuragi, Tomoaki Ikeda, Isao Date, Tetsuro Shingo, Takao Yasuhara, Kenichi Mishima, Naoya Aoo, Kazuhiko Harada, Nobuaki Egashira, Katsunori Iwasaki, Michihiro Fujiwara, Tsuyomu Ikenoue

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Objective: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. Study design: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. Results: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 ± 0.1 versus 6.9 ± 0.1 (P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 ± 0.1 seconds versus 1.97 ± 0.09 seconds (P < .01); in the water maze test, average swimming length was 1120.0 ± 95.2 cm versus 841.6 ± 92.1 cm (P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. Conclusion: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group.

Original languageEnglish
Pages (from-to)1028-1037
Number of pages10
JournalAmerican Journal of Obstetrics and Gynecology
Volume192
Issue number4
DOIs
Publication statusPublished - Apr 2005

Keywords

  • Encapsulation
  • Glial cell line-derived neurotrophic factor
  • Hypoxia-ischemia
  • Learning impairment
  • Neonatal rat

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

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