Predictors of hemorrhagic transformation occurring in patients with cardioembolic ischemic stroke
DOI:
https://doi.org/10.15587/2519-4798.2016.72033Keywords:
cardioembolic stroke, acute stage, hemorrhagic transformation, Cathepsin D, AFO -leukocytes, oxidative stressAbstract
Aim. To specify the role of certain clinical factors, active forms of oxygen (AFO) and Cathepsin D as predictors of hemorrhagic transformation occurring at cardioembolic ischemic stroke (CEIS).
Methods. Clinical and neurological examination of 125 patients with CEIS in the acute stage was carried out. The number of leukocytes in the stage of apoptosis (АNV+-cells) and necrosis (PI+-cells), the number of leukocytes with high AFO intracellular content (AFO+-cells) and low mitochondrial membrane potential (MMP) (Mito+-cells), and Cathepsin D activity were determined.
Results. Clinical and laboratory characteristics of CEIS in patients with hemorrhagic transformation (HT) were determined. Both severe stroke, and disorders of consciousness, and large stroke volume-heart size, and SBP is over than 170 mm Hg refer to clinical factors associated with HT. The number of AFO+-leukocytes and Cathepsin D activity in blood serum during the first day of the disease should be used as additional markers to predict cardioembolic ischemic stroke hemorrhagic transformation. When the count of AFO+-leukocytes is over than 40 %, along with Cathepsin D total activity, higher than 4.5, and Cathepsin D free activity, higher than 3.5 nmol of tyrosine.
Conclusion. The number of leukocytes with high AFO intracellular content and Cathepsin D activity in blood serum during the first day of cardioembolic ischemic stroke can be predictors of hemorrhagic transformation progress. Determination of hemorrhagic transformation predictors should be carried out before the thrombolytic and anticoagulant therapy
References
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- 1. Bang, O. Y., Saver, J. L., Kim, S. J., Kim, G.-M., Chung, C.-S., Ovbiagele, B. et. al (2011). Collateral Flow Averts Hemorrhagic Transformation After Endovascular Therapy for Acute Ischemic Stroke. Stroke, 42 (8), 2235–2239. doi: 10.1161/strokeaha.110.604603
- 2. Tan, S., Wang, D., Liu, M., Zhang, S., Wu, B., Liu, B. (2014). Frequency and predictors of spontaneous hemorrhagic transformation in ischemic stroke and its association with prognosis. Journal of Neurology, 261 (5), 905–912. doi: 10.1007/s00415-014-7297-8
- 3. Nogueira, R. G., Gupta, R., Jovin, T. G., Levy, E. I., Liebeskind, D. S., Zaidat, O. O. et. al (2014). Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients. Journal of NeuroInterventional Surgery, 7 (1), 16–21. doi: 10.1136/neurintsurg-2013-010743
- 4. Zhang, J., Yang, Y., Sun, H., Xing, Y. (2014).Hemorrhagic transformation after cerebral infarction: current concepts and challenges. Ann Transl Med., 2 (8), 81. doi: 10.3978/j.issn.2305-5839.2014.08.08
- 5. Campos, M., García-Bonilla, L., Hernández-Guillamon, M., Barceló, V., Morancho, A., Quintana, M. et. al (2013). Combining Statins with Tissue Plasminogen Activator Treatment After Experimental and Human Stroke: A Safety Study on Hemorrhagic Transformation. CNS Neuroscience & Therapeutics, 19 (11), 863–870. doi: 10.1111/cns.12181
- 6. Inzitari, D., Giusti, B., Nencini, P., Gori, A. M., Nesi, M., Palumbo, V. et. al (2013). MMP9 Variation After Thrombolysis Is Associated With Hemorrhagic Transformation of Lesion and Death. Stroke, 44 (10), 2901–2903. doi: 10.1161/strokeaha.113.002274
- 7. Hoffmann, A., Bredno, J., Wendland, M. F., Derugin, N., Hom, J., Schuster, T. et. al (2012). MRI Blood–Brain Barrier Permeability Measurements to Predict Hemorrhagic Transformation in a Rat Model of Ischemic Stroke. Translational Stroke Research, 3 (4), 508–516. doi: 10.1007/s12975-012-0212-7
- 8. Nikiforova-Postnikova,T. A., Doronin, B. M., Peskov, S. A. (2014). Bloodserumcytokinesaspredictorsofhemorrhagictransformationofischemicstroke.ZhNevrolPsikhiatrImS.S.Korsakova,114, 20–26.
- 9. Lee, J.-H., Park, K.-Y., Shin, J.-H., Cha, J.-K., Kim, H.-Y., Kwon, J.-H. et. al (2010). Symptomatic Hemorrhagic Transformation and Its Predictors in Acute Ischemic Stroke with Atrial Fibrillation. European Neurology, 64 (4), 193–200. doi: 10.1159/000319048
- 10. Choi, K.-H., Park, M.-S., Kim, J.-T., Nam, T.-S., Choi, S.-M., Kim, B.-C. et. al (2011). The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke. European Journal of Neurology, 19 (4), 570–577. doi: 10.1111/j.1468-1331.2011.03564.x
- 11. Lee, J.-G., Lee, K. B., Jang, I.-M., Roh, H., Ahn, M.-Y., Woo, H.-Y., Hwang, H.-W. (2013). Low Glomerular Filtration Rate Increases Hemorrhagic Transformation in Acute Ischemic Stroke. Cerebrovascular Diseases, 35 (1), 53–59. doi: 10.1159/000345087
- 12. Zehendner, C. M., Luhmann, H. J., Kuhlmann, C. R. (2009). Studying the neurovascular unit: an improved blood–brain barrier model. Journal of Cerebral Blood Flow & Metabolism, 29 (12), 1879–1884. doi: 10.1038/jcbfm.2009.103
- 13. Adams, R. A., Passino, M., Sachs, B. D. et. al (2004).Fibrin mechanisms and functions in nervous system pathology. Mol Interv., 4 (3), 163–176.
- 14. Abbott, N. J., Rönnbäck, L., Hansson, E. (2006). Astrocyte–endothelial interactions at the blood–brain barrier. Nature Reviews Neuroscience, 7 (1), 41–53. doi: 10.1038/nrn1824
- 15. Raptis, S. Z., Shapiro, S. D., Simmons, P. M., Cheng, A. M., Pham, C. T. N. (2005). Serine Protease Cathepsin G Regulates Adhesion-Dependent Neutrophil Effector Functions by Modulating Integrin Clustering. Immunity, 22 (6), 679–691. doi: 10.1016/j.immuni.2005.03.015
- 16. Fukuda, S. (2004). Focal Cerebral Ischemia Induces Active Proteases That Degrade Microvascular Matrix. Stroke, 35 (4), 998–1004. doi: 10.1161/01.str.0000119383.76447.05
- 17. Tsubokawa, T., Solaroglu, I., Yatsushige, H., Cahill, J., Yata, K., Zhang, J. H. (2006). Cathepsin and Calpain Inhibitor E64d Attenuates Matrix Metalloproteinase-9 Activity After Focal Cerebral Ischemia in Rats. Stroke, 37(7), 1888–1894. doi:10.1161/01.str.0000227259.15506.24
- 18. Kelly, P. J., Morrow, J. D., Ning, M., Koroshetz, W., Lo, E. H., Terry, E. et. al (2007). Oxidative Stress and Matrix Metalloproteinase-9 in Acute Ischemic Stroke: The Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) Study. Stroke, 39(1), 100–104. doi:10.1161/strokeaha.107.488189
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