| Project/Area Number |
16390489
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Ehime University |
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Principal Investigator |
GYO Kiyofumi Ehime University, School of Medicine, Professor, 医学部, 教授 (00108383)
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| Co-Investigator(Kenkyū-buntansha) |
HATO Naohito Ehime University, University Hospital, Lecturer, 医学部附属病院, 講師 (60284410)
SHINOMORI Yusuke Ehime University, University Hospital, Lecturer, 医学部附属病院, 講師 (60335908)
白馬 伸洋 愛媛大学, 医学部附属病院, 講師 (70304623)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥12,600,000 (Direct Cost: ¥12,600,000)
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| Keywords | cochlear ischemia / Bax / connexin 26 / glutamate transporter / ginsenoside Rb1 / prosaposin / sudden onset hearing loss / stem cell / 内耳虚血 / 血管条病変 / NO / 活性化酸素 / 細胞移植 / GDNF / 急性難聴 / therapeutic time window / 血管条 / ラセン神経節 / 有毛細胞脱落 / アポトーシス / 細胞治療 |
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| Research Abstract |
Underlining mechanisms of an ischemic cochlear damage were investigated using Mongolian gerbils. The animals were subjected to ischemic insult by occluding the vertebral arteries bilaterally for 15 min. The ischemia caused severer damage at the basal turn than at the apical turn. At the spiral ganglion, the number of neurons decreased gradually by ischemic insult ; to be 71% of preischemic level at day 7. Bax, an apoptosis-related protein, was noted prominently at day 1, which gradually disappeared thereafter. At the stria vascularis, positive immunostaining for connexin 26 decreased on day 1, but recovered to some extent at day 4 and completely healed at day 7. At the organ of Corti, the auditory hair cells were sporadically damaged due to apoptotic process, more prominently in the inner hair cells. From a study with glutamate transporter knock-out mice, glutamate was proved to be a key substance in aggravating the ischemic cochlear damage.
Three treatment modalities were assessed in this study. 1.Ginsenoside Rb1, which belongs to Kanpo medicine, was proved effective in prevention of ischemic cochlear damage. 2.Prosaposin, which is know to have neurotrophic effects, was also effective in protecting the ischemic cochlear damage. Stem cells derived from bone marrow prevented ischemic damage of the hair cells and the spiral ganglion cells, probably via release of neurotrophic factors. However, they were not effective in facilitating regeneration of the hair cells.
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