Von Willebrand factor targeted thrombolysis in canine basilar artery occlusion Article Swipe
Arianna Carfora
,
Blake Holthaus
,
Simon Yacoub
,
Dominic Franceschelli
,
Matthew Joseph
,
M. Wesley Milks
,
Ian Mandybur
,
Cole Anderson
,
Catherine Lee
,
Allyson Huttinger
,
Mohammad Shujaat
,
Debra G. Wheeler
,
Bruce A. Sullenger
,
Shahid M. Nimjee
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3389/fneur.2024.1436291
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3389/fneur.2024.1436291
Background and purpose Posterior circulation strokes, accounting for 20% of acute ischemic strokes, significantly contribute to morbidity and mortality. Fibrinolysis by rtPA improves outcomes in stroke but the risk of intracranial hemorrhage limits benefit. Arterial recanalization of basilar artery occlusion by thrombolysis or endovascular thrombectomy improves outcomes in posterior circulation strokes. This study investigates a VWF-targeting RNA aptamer as a safer and more effective alternative to rtPA in a canine model. Materials and methods Autologous clots were placed into the basilar artery to induce stroke in 24 beagles. To compare reperfusion, 0.9 mg/kg rtPA, 0.5 mg/kg BB-031, or vehicle were administered 60 min after the initiation of occlusion. Digital subtraction angiography, laser speckle imaging and magnetic resonance imaging were used to assess recanalization, reperfusion and infarct volume, respectively. Results Treatment with BB-031 resulted in recanalization of the posterior circulation on digital subtraction angiography with no evidence of microembolism assessed at sacrifice. 66.5% of animals treated with BB-031 resulted in reperfusion with a TICI score of ≥1 whereas vehicle remained at TICI score 0 as did all but one rtPA animal at sacrifice. Improved perfusion was seen in the basilar artery and surrounding blood vessels visualized through the cranial window with laser speckle imaging to ~47% of its original baseline in BB-031 group compared to rtPA at 37% and vehicle at 22%. Finally, BB-031-treatment resulted in an approximate 32% mean infarct volume, significantly smaller on magnetic resonance imaging compared to 56% in vehicle treated and 48% with rtPA treatment. Conclusion Targeted inhibition of VWF by BB-031 increased recanalization and reperfusion, and reduced infarct volume in a canine model of BAO stroke. It represents a promising target based on preliminary results for treating acute ischemic stroke.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fneur.2024.1436291
- https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1436291/pdf
- OA Status
- gold
- Cited By
- 1
- References
- 42
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4403239944
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4403239944Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fneur.2024.1436291Digital Object Identifier
- Title
-
Von Willebrand factor targeted thrombolysis in canine basilar artery occlusionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-10-09Full publication date if available
- Authors
-
Arianna Carfora, Blake Holthaus, Simon Yacoub, Dominic Franceschelli, Matthew Joseph, M. Wesley Milks, Ian Mandybur, Cole Anderson, Catherine Lee, Allyson Huttinger, Mohammad Shujaat, Debra G. Wheeler, Bruce A. Sullenger, Shahid M. NimjeeList of authors in order
- Landing page
-
https://doi.org/10.3389/fneur.2024.1436291Publisher landing page
- PDF URL
-
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1436291/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1436291/pdfDirect OA link when available
- Concepts
-
Medicine, Basilar artery, Thrombolysis, Digital subtraction angiography, Stroke (engine), Cardiology, Magnetic resonance imaging, Magnetic resonance angiography, Internal medicine, Thrombus, Fibrinolysis, Occlusion, Angiography, Radiology, Myocardial infarction, Mechanical engineering, EngineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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42Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.66.5% | 151 |
| abstract_inverted_index.acute | 10, 281 |
| abstract_inverted_index.after | 103 |
| abstract_inverted_index.based | 275 |
| abstract_inverted_index.blood | 192 |
| abstract_inverted_index.clots | 75 |
| abstract_inverted_index.group | 211 |
| abstract_inverted_index.laser | 111, 200 |
| abstract_inverted_index.mg/kg | 92, 95 |
| abstract_inverted_index.model | 266 |
| abstract_inverted_index.rtPA, | 93 |
| abstract_inverted_index.safer | 60 |
| abstract_inverted_index.score | 163, 171 |
| abstract_inverted_index.study | 52 |
| abstract_inverted_index.BB-031 | 131, 156, 210, 254 |
| abstract_inverted_index.animal | 179 |
| abstract_inverted_index.artery | 38, 81, 189 |
| abstract_inverted_index.assess | 121 |
| abstract_inverted_index.canine | 69, 265 |
| abstract_inverted_index.induce | 83 |
| abstract_inverted_index.limits | 32 |
| abstract_inverted_index.model. | 70 |
| abstract_inverted_index.placed | 77 |
| abstract_inverted_index.stroke | 25, 84 |
| abstract_inverted_index.target | 274 |
| abstract_inverted_index.volume | 262 |
| abstract_inverted_index.window | 198 |
| abstract_inverted_index.BB-031, | 96 |
| abstract_inverted_index.Digital | 108 |
| abstract_inverted_index.Results | 128 |
| abstract_inverted_index.animals | 153 |
| abstract_inverted_index.aptamer | 57 |
| abstract_inverted_index.basilar | 37, 80, 188 |
| abstract_inverted_index.compare | 89 |
| abstract_inverted_index.cranial | 197 |
| abstract_inverted_index.digital | 140 |
| abstract_inverted_index.imaging | 113, 117, 202, 236 |
| abstract_inverted_index.infarct | 125, 229, 261 |
| abstract_inverted_index.methods | 73 |
| abstract_inverted_index.purpose | 2 |
| abstract_inverted_index.reduced | 260 |
| abstract_inverted_index.results | 278 |
| abstract_inverted_index.smaller | 232 |
| abstract_inverted_index.speckle | 112, 201 |
| abstract_inverted_index.stroke. | 269, 283 |
| abstract_inverted_index.through | 195 |
| abstract_inverted_index.treated | 154, 242 |
| abstract_inverted_index.vehicle | 98, 167, 218, 241 |
| abstract_inverted_index.vessels | 193 |
| abstract_inverted_index.volume, | 126, 230 |
| abstract_inverted_index.whereas | 166 |
| abstract_inverted_index.Arterial | 34 |
| abstract_inverted_index.Finally, | 221 |
| abstract_inverted_index.Improved | 182 |
| abstract_inverted_index.Targeted | 249 |
| abstract_inverted_index.assessed | 148 |
| abstract_inverted_index.baseline | 208 |
| abstract_inverted_index.beagles. | 87 |
| abstract_inverted_index.benefit. | 33 |
| abstract_inverted_index.compared | 212, 237 |
| abstract_inverted_index.evidence | 145 |
| abstract_inverted_index.improves | 22, 45 |
| abstract_inverted_index.ischemic | 11, 282 |
| abstract_inverted_index.magnetic | 115, 234 |
| abstract_inverted_index.original | 207 |
| abstract_inverted_index.outcomes | 23, 46 |
| abstract_inverted_index.remained | 168 |
| abstract_inverted_index.resulted | 132, 157, 223 |
| abstract_inverted_index.strokes, | 5, 12 |
| abstract_inverted_index.strokes. | 50 |
| abstract_inverted_index.treating | 280 |
| abstract_inverted_index.Materials | 71 |
| abstract_inverted_index.Posterior | 3 |
| abstract_inverted_index.Treatment | 129 |
| abstract_inverted_index.effective | 63 |
| abstract_inverted_index.increased | 255 |
| abstract_inverted_index.morbidity | 16 |
| abstract_inverted_index.occlusion | 39 |
| abstract_inverted_index.perfusion | 183 |
| abstract_inverted_index.posterior | 48, 137 |
| abstract_inverted_index.promising | 273 |
| abstract_inverted_index.resonance | 116, 235 |
| abstract_inverted_index.Autologous | 74 |
| abstract_inverted_index.Background | 0 |
| abstract_inverted_index.Conclusion | 248 |
| abstract_inverted_index.accounting | 6 |
| abstract_inverted_index.contribute | 14 |
| abstract_inverted_index.hemorrhage | 31 |
| abstract_inverted_index.inhibition | 250 |
| abstract_inverted_index.initiation | 105 |
| abstract_inverted_index.mortality. | 18 |
| abstract_inverted_index.occlusion. | 107 |
| abstract_inverted_index.represents | 271 |
| abstract_inverted_index.sacrifice. | 150, 181 |
| abstract_inverted_index.treatment. | 247 |
| abstract_inverted_index.visualized | 194 |
| abstract_inverted_index.alternative | 64 |
| abstract_inverted_index.angiography | 142 |
| abstract_inverted_index.approximate | 226 |
| abstract_inverted_index.circulation | 4, 49, 138 |
| abstract_inverted_index.preliminary | 277 |
| abstract_inverted_index.reperfusion | 123, 159 |
| abstract_inverted_index.subtraction | 109, 141 |
| abstract_inverted_index.surrounding | 191 |
| abstract_inverted_index.Fibrinolysis | 19 |
| abstract_inverted_index.administered | 100 |
| abstract_inverted_index.angiography, | 110 |
| abstract_inverted_index.endovascular | 43 |
| abstract_inverted_index.intracranial | 30 |
| abstract_inverted_index.investigates | 53 |
| abstract_inverted_index.reperfusion, | 90, 258 |
| abstract_inverted_index.thrombectomy | 44 |
| abstract_inverted_index.thrombolysis | 41 |
| abstract_inverted_index.VWF-targeting | 55 |
| abstract_inverted_index.microembolism | 147 |
| abstract_inverted_index.respectively. | 127 |
| abstract_inverted_index.significantly | 13, 231 |
| abstract_inverted_index.recanalization | 35, 134, 256 |
| abstract_inverted_index.recanalization, | 122 |
| abstract_inverted_index.BB-031-treatment | 222 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5008694955 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 14 |
| corresponding_institution_ids | https://openalex.org/I2802841970, https://openalex.org/I4210157890 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8799999952316284 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.70973329 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |