Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones
Abstract
:1. Introduction
2. Etiology and Pathophysiology of Ischemic Stroke
2.1. Excitotoxicity
2.2. Oxidative Stress
2.3. Neuroinflammation
2.4. Apoptosis
2.4.1. Ferroptosis
2.4.2. Necroptosis
2.4.3. Pyroptosis
2.4.4. Parthanatos
2.4.5. Phagoptosis
2.5. Autophagy
3. Current Therapies for Ischemic Stroke and Their Targets
3.1. Thrombolytics/Thrombolytic Agents
3.2. Adjunctive Therapies
3.2.1. Anti-Thrombotic Agents
3.2.2. Antiplatelet Therapy
3.2.3. Fibrinogen-Depleting Agents
3.3. Cellular Therapies for Ischemic Stroke: A Paradigm Approach
Limitations of Stem Cell Therapy and Way Forward
4. Emerging Neuroprotective Agents for Ischemic Stroke: Pathophysiology-Targeted Therapies
5. Future Perspectives: Drug Repurposing and Re-Designing
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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S/No | Identifier | Stem Cell Type | Study Centre | Study Aim | Clinical Trial Phase | Study Status |
---|---|---|---|---|---|---|
1 | NCT00875654 | Autologous mesenchymal stem cells | France, Europe | Feasibility and tolerance | Phase I | Completed |
2 | NCT05008588 | Umbilical cord mesenchymal stem cells (whole cell and conditioned medium) | Indonesia, Asia | Safety and Efficacy | Phase I/II | Ongoing |
3 | NCT02117635 | Allogeneic human neural stem cell | United Kingdom, Europe | Efficacy | Phase II | Completed |
4 | NCT01501773 | Autologous bone marrow stem cell | India, Asia | Safety, feasibility, and efficacy | Phase II | Completed |
5 | NCT04811651 | Umbilical cord-derived mesenchymal stem cells | China, Asia | Safety and efficacy | Phase II | Recruiting |
6 | NCT01716481 | Autologous mesenchymal stem cells | South Korea, Asia | Neuroprotection | Phase III | Completed |
7 | NCT04631406 | Neural stem cell | California, North America | Safety and tolerability profile | Phase I/II | Recruiting |
8 | NCT03356821 | Stromal cells (intranasal) | Netherlands, Europe. | Safety and feasibility | Phase I/II | Completed |
9 | NCT05292625 | Umbilical cord-derived MSC (intrathecal and intravenous) | Vietnam, Asia | Safety and efficacy | Phase I/II | Recruiting |
11 | NCT06138210 | Induced pluripotent stem cell | China, Asia | Safety and preliminary efficacy | Phase I | Starts 2024 |
12 | NCT00859014 | Autologous mononuclear bone marrow cells (intravenous) | Houston, North America | Safety and tolerability | Phase I | Completed |
13 | NCT02178657 | Autologous mononuclear bone marrow cells (intra-arterial) | Spain, Europe | Safety and neuroprotection | Phase II | Ongoing |
14 | NCT00950521 | CD34+ stem cell (intracerebral implantation) | Taiwan, Asia | Efficacy | Phase II | Completed |
15 | NCT00535197 | Autologous CD34+ subset bone marrow stem cell (intra-arterial infusion) | London, Europe | Safety and tolerability | Phase I/II | Completed |
Drugs | Drug Class | Approved Indication(s) | Pathophysiology Target(s) | |
---|---|---|---|---|
Wang et al., 2007 [155] | Amlodipine | Calcium channel blocker (CCB) | Hypertension, Angina | Excitotoxicity |
Smith et al., 2019 [162] | Azithromycin | Macrolide antibiotic | Sinusitis, conjunctivitis, community-acquired pneumonia | Neuroinflammation |
Cho & Kim, 2009 [134] | Citicoline | Neurotropic | Parkinsonism, head injury | Apoptosis |
Forsse et al., 2019 [139] | Cyclosporin A | Immunomodulator | Post-transplant immunosuppression | Mitochondrial dysfunction secondary to oxidative stress and excitotoxicity |
Selim et al., 2009 [131] | Deferoxamine | Chelate | Iron poisoning | Excitotoxicity, oxidative stress, ferroptosis |
King et al., 2018 [152] | Glyburide | Sulfonylureas antidiabetic | Diabetes mellitus | Neuroinflammation and oxidative stress |
Zhao et al., 2019 [151] | Metformin | Biguanide antidiabetic | Diabetes mellitus, polycystic ovary syndrome | Neuroinflammation and oxidative stress |
Kikuchi et al., 2012 [164] | Minocycline | Tetracycline antibiotic | Inflammatory acne, gonococcal infections, urinary tract infection | Excitotoxicity, neuroinflammation, apoptosis, and oxidative stress |
Anttila et al., 2018 [167] | Naloxone | Opioid receptor antagonist | Opioid overdose | Neuroinflammation |
Staal et al., 2017 [161] | Senicapoc | Calcium-dependent potassium channel (KCa3.1) blocker | Sickle cell anemia | Neuroinflammation |
Twede et al., 2009 [156] | Ziconotide | Conopeptide, analgesic, N-type CCB | Chronic intractable pain | Excitotoxicity |
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Salaudeen, M.A.; Bello, N.; Danraka, R.N.; Ammani, M.L. Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones. Biomolecules 2024, 14, 305. https://doi.org/10.3390/biom14030305
Salaudeen MA, Bello N, Danraka RN, Ammani ML. Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones. Biomolecules. 2024; 14(3):305. https://doi.org/10.3390/biom14030305
Chicago/Turabian StyleSalaudeen, Maryam A., Nura Bello, Rabiu N. Danraka, and Maryam L. Ammani. 2024. "Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones" Biomolecules 14, no. 3: 305. https://doi.org/10.3390/biom14030305