| Project/Area Number |
18390411
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | University of Fukui |
|---|
Principal Investigator |
BABA Hisatoshi University of Fukui, Faculty of Medicine, Professor (00165060)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Shigeru University of Fukui, Hospital, Associate Professor (80234821)
UCHIDA Kenzo University of Fukui, Hospital, Associate Professor (60273009)
FURUKAWA Shoei Gifu Pharmaceutical University, Faculty of pharmacy, Professor (90159129)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥14,610,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥9,800,000 (Direct Cost: ¥9,800,000)
|
|---|
| Keywords | spinal cord injury / gene transfer / regeneration / microarrav / neurotrophin / 脊髄 / 軸索再生因子 / DNAマイクロビーズアレイ / 遺伝子解析 / ラット / 網羅的遺伝子解析 / 脊髄再生因子 |
|---|
| Research Abstract |
Chronic mechanical compression of the spinal cord causes neural tissue damage, including loss of anterior horn cells around the level of injury. Exogenous delivery of neurotrophins to neuronal cells could provide neuroprotection to a spinal cord subjected to mechanical injury. We investigated the efficacy of retrograde gene delivery of adenoviral vector (AdV) carrying neurotrophin-3 (NT-3) gene into twy (twy/twy) mouse spinal cord anterior horn neurons with chronic and progressive mechanical compression at C1-C2 level. AdV-NT-3 was used for retrograde delivery via the sternomastoid muscle to the cervical spinal accessory motoneurons in 16-week-old adult twy mice with relatively mild spinal cord compression. Four weeks after the AdV-NT-3 or AdV-beta-galactosidase cDNA (LacZ) as a marker gene injection, the compressed cervical spinal cord was examined histologically, immunohistologically, and by immunoblot analysis. Immunoreactivity to NT-3 was significantly enhanced in the AdV-NT-3-injected twy mice compared with the AdV-LacZ-injected mice. The numbers of anterior horn neurons of Nissl-, choline acetyltransferase (ChAT)-, and trkC-stained and wheat germ agglutinin-horseradish peroxidase(WGA-HRP)-labeled neurons at the spinal cord level with maximum compression were significantly higher in AdV-NT-3-transfected than in AdV-LacZ-transfected twy mice. Retrograde NT-3 gene transfer to twy mouse anterior horn neurons increased neurite axonal length and arborization of WGA-HRP-labeled neurons. Our results suggest that targeted retrograde NT-3 gene delivery is feasible in the intact animal and that it enhances neuronal survival even under chronic mechanical compression of the spinal cord. (c) 2008Wiley-Liss, Inc.
|
