title: ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion.
abstract: 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.
authors: Department of Emergency and Critical Care Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.
authors: Masayuki
authors: M
authors: Fujioka
authors: Kazuhide
authors: K
authors: Hayakawa
authors: Kenichi
authors: K
authors: Mishima
authors: Ai
authors: A
authors: Kunizawa
authors: Keiichi
authors: K
authors: Irie
authors: Sei
authors: S
authors: Higuchi
authors: Takafumi
authors: T
authors: Nakano
authors: Carl
authors: C
authors: Muroi
authors: Hidetada
authors: H
authors: Fukushima
authors: Mitsuhiko
authors: M
authors: Sugimoto
authors: Fumiaki
authors: F
authors: Banno
authors: Koichi
authors: K
authors: Kokame
authors: Toshiyuki
authors: T
authors: Miyata
authors: Michihiro
authors: M
authors: Fujiwara
authors: Kazuo
authors: K
authors: Okuchi
authors: Kenji
authors: K
authors: Nishio
mesh_terms: D000071120:ADAMTS13 Protein; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D002560:Cerebrovascular Circulation / Q000187:drug effects; D017353:Gene Deletion; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D013997:Time Factors; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D014841:von Willebrand Factor; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein