Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models
Abstract
:1. Stroke
2. Ischemic Stroke
2.1. Risk Factors
2.2. Diagnosis
2.3. Key Concept: Core and Penumbra
2.4. Ischemic Stroke Pathophysiology
2.5. Treatments
2.5.1. Thrombolysis
2.5.2. Mechanical Thrombectomy
2.5.3. Neuroprotective Drugs
2.6. Models for Acute Ischemic Stroke
2.6.1. In Vitro Models for AIS
2.6.2. In Vivo Models for Acute Ischemic Stroke
3. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Trial | Therapeutic Drug | Mechanism of Action | Status of Clinical Trial |
---|---|---|---|
VENUS (Phase III) | Nimodipine | Blocks voltage-gated channels (calcium) | Terminated: not effective |
MAVARIC (Phase I) | Verapamil (with magnesium sulfate) | Blocks of voltage-gated channels (calcium), after reperfusion | Results not published yet |
ESCAPE-NA1 (Phase III) | Nerinetide (Na-1) | Inhibits neuronal excitotoxicity | Approved by American FDA alone; but it does not display protection together with IVT |
ESCAPE-NEXT (Phase III) | Nerinetide (Na-1) together with EVT therapy | Inhibits neuronal excitotoxicity | Ongoing (completes in August 2023) |
URICO-ICTUS (Phase III) | Uric Acid (UA) | Antioxidant agent (reduces inflammation) | Small study sample, but a confirmatory trial is planned |
BAST (Phase III) | 3-N-butylphtalide (NBP) | Free radical scavenger (reduces inflammation) | Ongoing (completed on 31 December 2022), good outcome so far |
Evaluation of HUK in AIS (Phase IV) | Human Urinary Kallidinogenase (HUK) | Anti-inflammatory agents suppress TLR4/NF-kB pathway | Approved by China’s FDA, with post-approval surveillance ongoing |
A study of allogeneic mesenchymal bone marrow cells in AIS (Phase I/II) | Allogeneic adult mesenchymal bone marrow cells | Cell-based therapy | Completed, presented beneficial behavioral outcomes for patients |
J-REPAIR (Phase I/II) | JTR-161 (allogeneic stem cell product) | Cell-based therapy | Last updated on June 2022, results not published yet |
Efficacy and safety of FTY720 for AIS (phase II) | Fingolimod (FTY720) | Immune modulator | Completed; reduced injury and improved clinical outcomes |
Combination of the immune modulator Dimethyl Fumarate with alteplase in AIS (phase I/II) | Dimethyl Fumarate | Immune modulator | Ongoing (completes in December 2022) |
Cellular Source | Culture Conditions | Advantages | Disadvantages | |
---|---|---|---|---|
Spheroids | Differentiated cells, multicellular mixture, primary cells | Cultures with or without ECM and growth factors, self-assemble on heterogenous sphere format |
|
|
Organoids | Only stem cells: embryonic, adult, or pluripotent | Require ECM and growth factors, self-assemble with different cell lineages, resembling the structure and function of an organ |
|
|
In vivo Stroke Model | Advantages | Disadvantages |
---|---|---|
A. Intraluminal suture MCAO model |
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B. Electrocoagulation of MCA model |
|
|
C. Embolic stroke model |
|
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D. Endothelin-1 model |
|
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E. Photothrombosis model |
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Amado, B.; Melo, L.; Pinto, R.; Lobo, A.; Barros, P.; Gomes, J.R. Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models. Biomedicines 2022, 10, 2561. https://doi.org/10.3390/biomedicines10102561
Amado B, Melo L, Pinto R, Lobo A, Barros P, Gomes JR. Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models. Biomedicines. 2022; 10(10):2561. https://doi.org/10.3390/biomedicines10102561
Chicago/Turabian StyleAmado, Beatriz, Lúcia Melo, Raquel Pinto, Andrea Lobo, Pedro Barros, and João R. Gomes. 2022. "Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models" Biomedicines 10, no. 10: 2561. https://doi.org/10.3390/biomedicines10102561