ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion

被引：105

作者：

Fujioka, Masayuki ^{[1
,2
,3
]}

Hayakawa, Kazuhide ^{[2
]}

Mishima, Kenichi ^{[2
]}

Kunizawa, Ai ^{[3
]}

Irie, Keiichi ^{[2
]}

Higuchi, Sei ^{[2
]}

Nakano, Takafumi ^{[2
]}

Muroi, Carl ^{[3
]}

Fukushima, Hidetada ^{[1
]}

Sugimoto, Mitsuhiko ^{[4
]}

Banno, Fumiaki ^{[5
]}

Kokame, Koichi ^{[5
]}

Miyata, Toshiyuki ^{[5
]}

Fujiwara, Michihiro ^{[2
]}

Okuchi, Kazuo ^{[1
]}

Nishio, Kenji ^{[1
]}

机构：

[1] Nara Med Univ, Dept Emergency & Crit Care Med, Nara 6348522, Japan

[2] Fukuoka Univ, Fac Pharmaceut Sci, Dept Neuropharmacol, Fukuoka 81401, Japan

[3] Tech Univ Dresden, Stroke Ctr, Helios Gen Hosp Aue, Saxony, Germany

[4] Nara Med Univ, Dept Regulatory Med Thrombosis, Nara 6348522, Japan

[5] Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 565, Japan

来源：

BLOOD | 2010年 / 115卷 / 08期

关键词：

VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; ENDOTHELIAL-CELL-INTERACTIONS; CEREBRAL-ARTERY OCCLUSION; BLOOD-FLOW; DELAYED TREATMENT; FACTOR STRINGS; SHEAR-STRESS; NO-REFLOW; STROKE;

D O I：

10.1182/blood-2009-06-230110

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib-von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13(-/-) and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13(-/-) mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13(-/-) compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke. (Blood. 2010;115:1650-1653)

引用

页码：1650 / 1653

页数：4

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