Evaluation of riluzole therapy using the glutamate segmental infusion model. - Development of pharmacologic spinal cord protection for amyotrophic lateral screlosis (ALS) -
| Project/Area Number |
12671327
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Keio University |
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Principal Investigator |
UEDA Toshihiko School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (20138035)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Gulutamate / Amyotrophic lateral screlosis / Rilusole / NBQX / AMPA / kainite receptor / Experimental model / spinal cord protection / Glutamate segmental infusion model / Glutamate neurotoxicity / 脊髄 / 実験動物モデル |
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| Research Abstract |
Amyotrophic lateral screlosis (ALS) is a progressive motor neuron disease for which there is no adequate treatment. The antiglutamate agent riluzole was reported to slow the progression of ALS in clinical prospective controlled study. Using the segmental glutamate infusion model, we evaluated protective effects of riluzole and NBQX, which is an AMPA/kainate antagonist, to spinal cord in vivo. Method; Infrarenal isolation was performed in New Zealand white rabbits (3.5-4.0kg). Group A animals (n=7) were orally treated with riluzole (100mg/kg/day) for ten days before surgery. Group B animals (n=7) were fed without riluzole. Glutamate solution (50mM) was infused to the isolated abdomial aortic segment at a rate of two ml/min for 5 minutes. Group C (n=8) and group D (n=8) animals received riluzole (100mg/kg/day) for ten days. Group E (n=8) animals were fed without riluzole. Group D and group E animals were pretreated with NBQX (4 mg/kg), followed by the infusion of glutamate (50mM) for 5 minutes. Group C animals received vehicle, followed by the glutamate infusion in the same manner. Neurologic status was assessed using the Tarlov system. Results; Neurologic scores in group A, group B were 3.7±1.6 and 0.8±0.6 respectively. Group A animals exhibited better neurologic recovery compared with group B significantly (p<0.05). Neurologic scores in group C, group D, and group E were 3.2±0.6, 4.1±0.5 and 2.3±0.7 respectively. Group D animals exhibited better neurologic recovery compared with group C and group E significantly (p<0.05). Conclusion; Riluzole combined with NBQX can improve spinal cord recovery in the segmental glutamate infusion model.
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Report
(3 results)
Research Products
(20 results)
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[Publications] Mori A, Ueda T, Shimizu, H, Nakamiehi T, Yasudo M, Cho Y, Moro K, Kawada S: "Glutamate neurotoxicity in spinal cord injury. ln: Kawada S, Ueda T, Shimizu H, eds. Cardio-aortic and aortic surgery. (Keio University International Symposia for Life of Science and Medicine Vol. 7)"Tokyo Springe Verlag. 190-197 (2001)
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