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: Masayuki Fujioka, Kazuhide Hayakawa, Kenichi Mishima, Ai Kunizawa, Keiichi Irie, Sei Higuchi, Takafumi Nakano, Carl Muroi, Hidetada Fukushima, Mitsuhiko Sugimoto, Fumiaki Banno, Koichi Kokame, Toshiyuki Miyata, Michihiro Fujiwara, Kazuo Okuchi, Kenji Nishio
• Journal: Blood (Blood) Vol. 115 Issue 8 Pg. 1650-3 (Feb 25 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 19965676 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• von Willebrand Factor
• ADAMTS13 protein, mouse
• Metalloendopeptidases
• ADAMTS13 Protein

Topics

• ADAMTS13 Protein
• Animals
• Brain Ischemia (drug therapy, enzymology, genetics)
• Cerebrovascular Circulation (drug effects)
• Gene Deletion
• Metalloendopeptidases (genetics, metabolism, therapeutic use)
• Mice
• Mice, Knockout
• Neuroprotective Agents (metabolism, therapeutic use)
• Reperfusion Injury (drug therapy, enzymology, genetics)
• Stroke (drug therapy, enzymology, genetics)
• Time Factors
• von Willebrand Factor (genetics, metabolism)