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Prospective clinical biomarkers of caspase-mediated apoptosis associated with neuronal and neurovascular damage following stroke and other severe brain injuries: Implications for chronic neurodegeneration
Olena Y Glushakova1, Andriy A Glushakov2, Dayanjan S Wijesinghe3, Alex B Valadka1, Ronald L Hayes4, Alexander V Glushakov5
1 Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA
2 Department of Neurosurgery, University of South Florida College of Medicine, Tampa, FL, USA
3 Department of Pharmacotherapy and Outcomes Sciences, Laboratory of Pharmacometabolomics and Companion Diagnostics, Virginia Commonwealth University, Richmond, VA, USA
4 Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA; Banyan Biomarkers, Inc., Alachua, 32615, USA
5 Single Breath, Inc., Gainesville, FL, USA
Correspondence Address:
Alexander V Glushakov
Single Breath, Inc., Gainesville, FL
USA
Olena Y Glushakova
Department of Neurosurgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/bc.bc_27_16
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Acute brain injuries, including ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI), are major worldwide health concerns with very limited options for effective diagnosis and treatment. Stroke and TBI pose an increased risk for the development of chronic neurodegenerative diseases, notably chronic traumatic encephalopathy, Alzheimer's disease, and Parkinson's disease. The existence of premorbid neurodegenerative diseases can exacerbate the severity and prognosis of acute brain injuries. Apoptosis involving caspase-3 is one of the most common mechanisms involved in the etiopathology of both acute and chronic neurological and neurodegenerative diseases, suggesting a relationship between these disorders. Over the past two decades, several clinical biomarkers of apoptosis have been identified in cerebrospinal fluid and peripheral blood following ischemic stroke, intracerebral and subarachnoid hemorrhage, and TBI. These biomarkers include selected caspases, notably caspase-3 and its specific cleavage products such as caspase-cleaved cytokeratin-18, caspase-cleaved tau, and a caspase-specific 120 kDa αII-spectrin breakdown product. The levels of these biomarkers might be a valuable tool for the identification of pathological pathways such as apoptosis and inflammation involved in injury progression, assessment of injury severity, and prediction of clinical outcomes. This review focuses on clinical studies involving biomarkers of caspase-3-mediated pathways, following stroke and TBI. The review further examines their prospective diagnostic utility, as well as clinical utility for improved personalized treatment of stroke and TBI patients and the development of prophylactic treatment chronic neurodegenerative disease. |
