Multiphase adjuvant neuroprotection: A novel paradigm for improving acute ischemic stroke outcomes

While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete...

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Published inBrain circulation Vol. 6; no. 1; pp. 11 - 18
Main Authors Zhao, Wenbo, Wu, Chuanjie, Dornbos III, David, Li, Sijie, Song, Haiqing, Wang, Yuping, Ding, Yuchuan, Ji, Xunming
Format Journal Article
LanguageEnglish
Published India Wolters Kluwer India Pvt. Ltd 01.01.2020
Medknow Publications and Media Pvt. Ltd
Medknow Publications & Media Pvt. Ltd
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ISSN2394-8108
2455-4626
2455-4626
DOI10.4103/bc.bc_58_19

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Abstract While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of "Multiphase Adjuvant Neuroprotection" as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.
AbstractList While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of “Multiphase Adjuvant Neuroprotection” as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.
While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of "Multiphase Adjuvant Neuroprotection" as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of "Multiphase Adjuvant Neuroprotection" as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.
Audience Academic
Author Wu, Chuanjie
Li, Sijie
Ji, Xunming
Ding, Yuchuan
Song, Haiqing
Wang, Yuping
Zhao, Wenbo
Dornbos III, David
AuthorAffiliation 2 Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
3 Department of Neurological Surgery, Semmes-Murphey Clinic and University of Tennessee Health Science Center, Memphis, TN, USA
1 Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
4 China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
5 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
AuthorAffiliation_xml – name: 4 China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China
– name: 5 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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– name: 1 Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
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  organization: Department of Neurology; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing
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  givenname: Chuanjie
  surname: Wu
  fullname: Wu, Chuanjie
  organization: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing
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  fullname: Dornbos III, David
  organization: Department of Neurological Surgery, Semmes-Murphey Clinic and University of Tennessee Health Science Center, Memphis, TN
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  surname: Li
  fullname: Li, Sijie
  organization: Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing
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  givenname: Haiqing
  surname: Song
  fullname: Song, Haiqing
  organization: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing
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  surname: Wang
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  organization: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing
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  surname: Ding
  fullname: Ding, Yuchuan
  organization: China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing
– sequence: 8
  givenname: Xunming
  surname: Ji
  fullname: Ji, Xunming
  organization: Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine; China-America Institute of Neuroscience; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32166195$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords penumbra
reperfusion injury
endovascular thrombectomy
Acute ischemic stroke
neuroprotection
Language English
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Snippet While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by...
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SubjectTerms acute ischemic stroke
Apoptosis
Clinical trials
Edema
Embolization
endovascular thrombectomy
Ischemia
Low income groups
neuroprotection
penumbra
Prognosis
Reperfusion injury
Review
Stents
Stroke
Tirofiban
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Title Multiphase adjuvant neuroprotection: A novel paradigm for improving acute ischemic stroke outcomes
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