2004 Fiscal Year Final Research Report Summary
Neuroprotective effects of synthetic pyrimidine compound in focal cerebral ischemia
| Project/Area Number |
14571337
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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 |
Cerebral neurosurgery
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
KAWAMATA Takakazu Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (90204768)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Tomokatsu Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (60010443)
YAMANE Fumitaka Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (60210506)
NAKAJIMA Hiroshi Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80227800)
NAKAMURA Satoshi Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (20266779)
MITSUYAMA Tetsuryu Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (80318104)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Cerebral ischemia / Cerebral infarction / Pyrimidine compound / MS-818 / Neurological dysfunction / Stroke |
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| Research Abstract |
MS-818(2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is a synthetic heterocyclic pyrimidine compound reported to have a variety of biological activities including neurite outgrowth, astrocyte differentiation, suppression of neuronal apoptosis, regeneration of injured peripheral nerves, fracture repairs, angiogenesis and superovulation. Aiming to exploit the neurotrophic effects of MS-818, we evaluated the effect of the synthetic pyrimidine derivative on infarct volume reduction and amelioration of sensorimotor dysfunction in a rat model of focal ischemia.
Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. MS-818(1,5,or 10 mg/kg) or phosphate buffered saline (control group)(totally 4 groups ; n=10 in each group) was administered intraperitoneally at the time of ischemic onset and 24 hours later. Rats were killed at 48 hours after the stroke surgery, and infarct volume was determined by an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Postischemic neurological deficit and body weight were also assessed.
Significant infarct volume reductions (total and cortical infarction) were found in the all the MS-818 groups compared with the control group. Furthermore, MS-818 induced significant amelioration of sensorimotor function in forelimb and hindlimb placing tests. The present findings suggest that MS-818,which has a much smaller molecular weight than neurotrophic peptides, represent a new approach to the treatment of focal cerebral ischemia.
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