2010 Fiscal Year Final Research Report
Ischemic neuropathy : pathogenesis and treatment
| Project/Area Number |
20591037
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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 |
Neurology
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| Research Institution | The Nukada Institute for Medical and Biological Reseach |
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Principal Investigator |
NUKADA Hitoshi The Nukada Institute for Medical and Biological Reseach, 副理事長 (60118833)
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| Co-Investigator(Kenkyū-buntansha) |
YAGIHASHI Soroku 弘前大学, 医学系医学科, 教授 (40111231)
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| Co-Investigator(Renkei-kenkyūsha) |
BABA Masayuki 青森県立中央病院, 神経内科
TSUTIHARA Toyokazu 防衛医科大学校, 整形外科
NEMOTO Kouichi 防衛医科大学校, 整形外科
NARUSE Keiko 愛知学院大学, 内科
NAKAMURA Jiro 名古屋大学, 内科
MARCUS Mueller Muenster大学, 神経内科
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| Research Collaborator |
OGASAWARA Saori 弘前大学, 第一病理
TSUJI Mari 弘前大学, 第一病理
DENIDE McMorran オタゴ大学, 内科
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| Project Period (FY) |
2008 – 2010
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| Keywords | 虚血性末梢神経障害 / 糖尿病性末梢神経障害 / 虚血・再灌流傷害 / 高血圧 / マクロファージ / HGF遺伝子治療 |
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| Research Abstract |
1) In diabetes, hypertension compounds and greatly increases the risk of microvascular complications. Hypertension directly damages the microvasculature. However, it is uncertain whether hypertension, per se, causes neuropathy, and how hypertension affects diabetic neuropathy. We have found neuropathic abnormalities in hypertensive rats, and also demonstrated that the severity of neuropathy in diabetes with hypertension was greater than neuropathy in non-hypertensive diabetes. Uncontrolled hypertension could cause neuropathy, and hypertension enhances the severity of diabetic neuropathy. In addition, we have shown that increased susceptibility to ischemia and reperfusion in hypertensive rats.
2) Ischemic vulnerability in diabetic nerve plays a paramount role in the development of diabetic neuropathy, yet little is known of the underlying mechanism. We conclude that macrophage proliferation and activation occur in STZ-diabetic nerves. The acute inflammatory response after a short period of ischemia was intensified in diabetic nerves. Activation of resident macrophages and infiltration by recruited macrophages could be casually linked to ischemic susceptibility in diabetic nerve.
3) Treatment of sensory symptoms in ischemic limbs resulting from peripheral artery disease is still unsatisfactory. We have found that HGF gene treatment improved sensory symptoms and blood flow in acute ischemic and reperfusion injury of rats.
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