Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication
Abstract
Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke.
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This astrocyte subcluster was enriched for genes involved in extracellular matrix organization, metabolic support, and inflammatory modulation.
“This subcluster was enriched for genes involved in extracellular matrix organization [102, 135, 136], metabolic support [135, 137], and inflammatory modulation [138–141].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [136]
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- Authors
- Nakano, T., Irie, K., Hayakawa, K., Sano, K., Nakamura, Y., Tanaka, M., Yamashita, Y., Satho, T., Fujioka, M., Muroi, C., Matsuo, K., Ishikura, H., Futagami, K., & Mishima, K.
- Affiliations
- Fukuoka University (JP)
- Fukuoka University Hospital (JP)
- Corresponding author
- Irie, Keiichi
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 1624
- Pages
- 330-335
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1441142084
- Cited by
- 32
- References
- 33
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 2
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26462170)
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- ADAMTS13, ischemic stroke, treatment delay, tissue plasminogen activator, therapeutic time window, cerebral hemorrhage, von Willebrand factor cleavage, HMGB1, infarct size, cerebral blood flow, middle cerebral artery occlusion, ischemia-reperfusion injury
- MeSH terms
- ADAMTS13 Protein, Animals, Cerebral Hemorrhage, Cerebral Infarction, Brain Ischemia, Cerebrovascular Circulation, Disease Models, Animal, Fibrinolytic Agents, Male, Mice, Inbred Strains, Neurologic Examination, Tissue Plasminogen Activator, Time Factors, Laser-Doppler Flowmetry, HMGB1 Protein, Mice, ADAM Proteins
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