ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion.
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.
Fujioka
Masayuki
M
Department of Emergency and Critical Care Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.
Hayakawa
Kazuhide
K
Mishima
Kenichi
K
Kunizawa
Ai
A
Irie
Keiichi
K
Higuchi
Sei
S
Nakano
Takafumi
T
Muroi
Carl
C
Fukushima
Hidetada
H
Sugimoto
Mitsuhiko
M
Banno
Fumiaki
F
Kokame
Koichi
K
Miyata
Toshiyuki
T
Fujiwara
Michihiro
M
Okuchi
Kazuo
K
Nishio
Kenji
K
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
D018696:Neuroprotective Agents; D014841:von Willebrand Factor; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein