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Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy

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Abstract

Ischemic stroke is one of the significant causes of morbidity and mortality, affecting millions of people across the globe. Cell injury in the infarct region is an inevitable consequence of focal cerebral ischemia. Subsequent reperfusion exacerbates the harmful effect and increases the infarct volume. These cellular injuries follow either a regulated pathway involving tightly structured signaling cascades and molecularly defined effector mechanisms or a non-regulated pathway, also known as accidental cell death, where the process is biologically uncontrolled. Classical cell death pathways are long established and well reported in several articles that majorly define apoptotic cell death. A recent focus on cell death study also considers investigation on non-classical pathways that are tightly regulated, may or may not involve caspases, but non-apoptotic. Pathological cell death is a cardinal feature of different neurodegenerative diseases. Although ischemia cannot be classified as a neurodegenerative disease, it is a cerebrovascular event where the infarct region exhibits aberrant cell death. Over the past few decades, several therapeutic options have been implicated for ischemic stroke. However, their use has been hampered owing to the number of limitations that they possess. Ischemic penumbral neurons undergo apoptosis and become dysfunctional; however, they are salvageable. Thus, understanding the role of different cell death pathways is crucial to aid in the modern treatment of protecting apoptotic neurons.

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Funding

Authors acknowledge the International Society for Neurochemistry (ISN) Return Home grant, Department of Pharmaceuticals, Ministry of Chemical and Fertilizers, Govt. of India, and National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, Gandhinagar, India.

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  1. Aishika Datta and Deepaneeta Sarmah contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, 382355, India

    Aishika Datta, Deepaneeta Sarmah, Leela Mounica, Harpreet Kaur, Radhika Kesharwani, Geetesh Verma, Pabbala Veeresh, Vignesh Kotian, Kiran Kalia & Pallab Bhattacharya

  2. Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India

    Anupom Borah

  3. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Xin Wang

  4. Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

    Kunjan R. Dave

  5. Department of Neurology and Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Dileep R. Yavagal

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Datta, A., Sarmah, D., Mounica, L. et al. Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy. Transl. Stroke Res. 11, 1185–1202 (2020). https://doi.org/10.1007/s12975-020-00806-z

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