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Effects of Mild and Moderate Hypothemia Therapy on Expression of Cerebral Neuron Apoptosis Related Proteins and Glial Fiber Acidic Protein After Rat Cardio-pulmonary Resuscitation

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Abstract

To explore the effects of different degrees of hypothermia on brain tissue apoptosis after cardio-pulmonary resuscitation (CPR). Cardiac arrest for 5 min induced by asphyxia method was used to create CPR model. 30 SD rats were randomly divided into control group (normothermia), 33 °C hypothermia group and 30 °C hypothermia group with ten rats in each. Rats in control group received routine treatment at 25 °C room temperature after CPR; Rats in mild hypothermia and moderate hypothermia groups were given hypothermia treatment 0.5 h after CPR. Brain tissue in all groups was taken 24 h after CPR, and immunohistochemistry was used to detect the caspase-3 in cerebral cortex and glial fiber acidic protein (GFAP) expression in astrocyte. Western blotting was used to detect Bcl-2 and Bax protein expression, and histopathological change was observed in brain tissue. Compare to the control group, caspase-3 expression in cerebral neurons in hypothermia group was significantly decreased (p<0.01), which was significantly lower in 30 °C group than that in 33 °C group (p > 0.05); GFAP level in hypothermia groups was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); Bcl-2 expression level in hypothermia group was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); The level of Bax had no significant difference among the three groups. Hypothermia-regulated GFAP expression by decreasing caspase-3 expression and increasing Bcl-2 expression to promote brain cell signaling transduction, and further inhibited cell apoptosis and reduced brain injury. Moderate hypothermia therapy is more effective than mild hypothermia in preventing brain injure.

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Bibliography

  1. Diskin, F. J., Camp-Rogers, T., Peberdy, M. A., Ornato, J. P., Kurz, M. C. (2014). External validation of termination of resuscitation guidelines in the setting of intra-arrest cold saline, mechanical CPR, and comprehensive post resuscitation care. Resuscitation, 85(7), 910–914.

  2. Mangla, A., Daya, M. R., & Gupta, S. (2014). Post-resuscitation care for survivors of cardiac arrest. Indian heart journal, 66, S105–S112.

    Article  PubMed  Google Scholar 

  3. Pallas Beneyto, L. A., Rodriguez Luis, O., & Miguel Bayarri, V. (2012). In hospital cardio-cerebral resuscitation. Medicina Clinica, 138(3), 120–126.

    Article  PubMed  Google Scholar 

  4. Lu, X., Ma, L., Sun, S., Xu, J., Zhu, C., & Tang, W. (2014). The effects of the rate of postresuscitation rewarming following hypothermia on outcomes of cardiopulmonary resuscitation in a rat model. Critical Care Medicine, 42(2), e106–e113.

    Article  PubMed  Google Scholar 

  5. Souza, L. L., Duchene, J., Todiras, M., Azevedo, L. C., Costa-Neto, C. M., Alenina, N., et al. (2014). Receptor MAS protects mice against hypothermia and mortality induced by endotoxemia. Shock, 41(4), 331–336.

    Article  CAS  PubMed  Google Scholar 

  6. Gong, P., Hua, R., Zhang, Y., Zhao, H., Tang, Z., Mei, X., et al. (2013). Hypothermia-induced neuroprotection is associated with reduced mitochondrial membrane permeability in a swine model of cardiac arrest. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 33(6), 928–934.

    Article  CAS  Google Scholar 

  7. Wiedemann, D., Kocher, A., Dorfmeister, M., Vadehra, A., Mahr, S., Laufer, G., et al. (2013). Effect of cerebral protection strategy on outcome of patients with Stanford type A aortic dissection. The Journal of thoracic and cardiovascular surgery, 146(3), 647–655. e641.

    Article  PubMed  Google Scholar 

  8. Mortberg, E., Zetterberg, H., Nordmark, J., Blennow, K., Rosengren, L., & Rubertsson, S. (2011). S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment. Resuscitation, 82(1), 26–31.

    Article  PubMed  Google Scholar 

  9. Wang, Q., Ishikawa, T., Michiue, T., Zhu, B. L., Guan, D. W., & Maeda, H. (2012). Evaluation of human brain damage in fatalities due to extreme environmental temperature by quantification of basic fibroblast growth factor (bFGF), glial fibrillary acidic protein (GFAP), S100beta and single-stranded DNA (ssDNA) immunoreactivities. Forensic Science International, 219(1–3), 259–264.

    Article  CAS  PubMed  Google Scholar 

  10. Testori, C., Sterz, F., Behringer, W., Haugk, M., Uray, T., Zeiner, A., et al. (2011). Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation, 82(9), 1162–1167.

    Article  PubMed  Google Scholar 

  11. Fink, E. L., Marco, C. D., Donovan, H. A., Alexander, H., Dixon, C. E., Jenkins, L. W., et al. (2005). Brief induced hypothermia improves outcome after asphyxial cardiopulmonary arrest in juvenile rats. Developmental Neuroscience, 27(2–4), 191–199.

    Article  CAS  PubMed  Google Scholar 

  12. Han, F., Boller, M., Guo, W., Merchant, R. M., Lampe, J. W., Smith, T. M., et al. (2010). A rodent model of emergency cardiopulmonary bypass resuscitation with different temperatures after asphyxial cardiac arrest. Resuscitation, 81(1), 93–99.

    Article  PubMed  Google Scholar 

  13. Sanders, A. B. (2006). Therapeutic hypothermia after cardiac arrest. Current opinion in critical care, 12(3), 213–217.

    Article  PubMed  Google Scholar 

  14. Meybohm, P., Gruenewald, M., Albrecht, M., Muller, C., Zitta, K., Foesel, N., et al. (2011). Pharmacological postconditioning with sevoflurane after cardiopulmonary resuscitation reduces myocardial dysfunction. Critical Care, 15(5), R241.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Zhao, H., Li, C. S., Gong, P., Tang, Z. R., Hua, R., Mei, X., et al. (2012). Molecular mechanisms of therapeutic hypothermia on neurological function in a swine model of cardiopulmonary resuscitation. Resuscitation, 83(7), 913–920.

    Article  CAS  PubMed  Google Scholar 

  16. Snyder, B. D., Ramirez-Lassepas, M., Sukhum, P., Fryd, D., & Sung, J. H. (1979). Failure of thiopental to modify global anoxic injury. Stroke; a journal of cerebral circulation, 10(2), 135–141.

    Article  CAS  PubMed  Google Scholar 

  17. Bernard, S. A., Gray, T. W., Buist, M. D., Jones, B. M., Silvester, W., Gutteridge, G., et al. (2002). Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. The New England journal of medicine, 346(8), 557–563.

    Article  PubMed  Google Scholar 

  18. Sakurai, T., Kudo, M., Watanabe, T., Itoh, K., Higashitsuji, H., Arizumi, T., et al. (2013). Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production. Digestive Diseases, 31(5–6), 440–446.

    Article  PubMed  Google Scholar 

  19. Kochanek, P. M., Drabek, T., & Tisherman, S. A. (2009). Therapeutic hypothermia: the Safar vision. Journal of Neurotrauma, 26(3), 417–420.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Schmitt, K. R., Boato, F., Diestel, A., Hechler, D., Kruglov, A., Berger, F., et al. (2010). Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha. Brain Pathology, 20(4), 771–779.

    Article  CAS  PubMed  Google Scholar 

  21. Bazan, N. G. (2009). Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Prostaglandins Leukotrienes and Essential Fatty Acids, 81(2–3), 205–211.

    Article  CAS  Google Scholar 

  22. Brambrink, A. M., Schneider, A., Noga, H., Astheimer, A., Gotz, B., Korner, I., et al. (2000). Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 20(10), 1425–1436.

    Article  CAS  Google Scholar 

  23. Xiang, J., Tang, Y. P., Zhou, Z. Y., Wu, P., Wang, Z., Mori, M., et al. (2010). Apocynum venetum leaf extract protects rat cortical neurons from injury induced by oxygen and glucose deprivation in vitro. Canadian Journal of Physiology and Pharmacology, 88(9), 907–917.

    Article  CAS  PubMed  Google Scholar 

  24. Phanithi, P. B., Yoshida, Y., Santana, A., Su, M., Kawamura, S., & Yasui, N. (2000). Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL. Neuropathology: Official Journal of the Japanese Society of Neuropathology, 20(4), 273–282.

    Article  CAS  Google Scholar 

  25. Zhang, Z., Sobel, R. A., Cheng, D., Steinberg, G. K., & Yenari, M. A. (2001). Mild hypothermia increases Bcl-2 protein expression following global cerebral ischemia. Brain Research. Molecular Brain Research, 95(1–2), 75–85.

    Article  CAS  PubMed  Google Scholar 

  26. Kim, F., Olsufka, M., Longstreth, W. T, Jr, Maynard, C., Carlbom, D., Deem, S., et al. (2007). Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation, 115(24), 3064–3070.

    Article  PubMed  Google Scholar 

  27. de Waard, M. C., Biermann, H., Brinckman, S. L., Appelman, Y. E., Driessen, R. H., Polderman, K. H., et al. (2013). Automated peritoneal lavage: an extremely rapid and safe way to induce hypothermia in post-resuscitation patients. Critical Care, 17(1), R31.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Chenoune, M., Lidouren, F., Adam, C., Pons, S., Darbera, L., Bruneval, P., et al. (2011). Ultrafast and whole-body cooling with total liquid ventilation induces favorable neurological and cardiac outcomes after cardiac arrest in rabbits. Circulation, 124(8), 901–9011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Broughton, B. R., Reutens, D. C., & Sobey, C. G. (2009). Apoptotic mechanisms after cerebral ischemia. Stroke; a Journal of Cerebral Circulation, 40(5), e331–e339.

    Article  PubMed  Google Scholar 

  30. Maier, C. M., Sun, G. H., Cheng, D., Yenari, M. A., Chan, P. H., & Steinberg, G. K. (2002). Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Neurobiology of Disease, 11(1), 28–42.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China

    Li Ding & Jianping Yang

  2. Department of Anesthesiology, The People’s Hospital of Yinzhou, Ningbo, Zhejiang, 315040, China

    Li Ding, Xiang Gao & Shenghui Yu

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  1. Li Ding
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  2. Xiang Gao
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Correspondence to Jianping Yang.

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Ding, L., Gao, X., Yu, S. et al. Effects of Mild and Moderate Hypothemia Therapy on Expression of Cerebral Neuron Apoptosis Related Proteins and Glial Fiber Acidic Protein After Rat Cardio-pulmonary Resuscitation. Cell Biochem Biophys 70, 1519–1525 (2014). https://doi.org/10.1007/s12013-014-0087-1

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