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Role of glucose-regulated protein 78 in early brain injury after experimental subarachnoid hemorrhage in rats

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Summary

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). This study investigated the role of glucose-regulated protein 78 (GRP78) in EBI after SAH. Male Sprague-Dawley rats (n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.

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References

  1. Friedrich B, Muller F, Feiler S, et al. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. J Cereb Blood Flow Metab, 2012,32(3):447–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kusaka G, Ishikawa M, Nanda A, et al. Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab, 2004,24(8): 916–925

    Article  CAS  PubMed  Google Scholar 

  3. Zhao H, Ji Z, Tang D, et al. Role of autophagy in early brain injury after subarachnoid hemorrhage in rats. Mol Biol Rep, 2013,40(2):819–827

    Article  CAS  PubMed  Google Scholar 

  4. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cel Biol, 2007,8(7):519–529

    Article  CAS  Google Scholar 

  5. Cao Y, Hao Y, Li H, et al. Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose. Int J Mol Med, 2014,33(4): 809–816

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Gules I, Satoh M, Clower BR, et al. Comparison of three rat models of cerebral vasospasm. Am J Physiol Heart Circ Physiol, 2002,283(6):H2551–2559

    Article  CAS  PubMed  Google Scholar 

  7. Garcia JH, Wagner S, Liu KF, et al. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke, 1995,26(4):627–634

    CAS  PubMed  Google Scholar 

  8. Sehba FA, Hou J, Pluta RM, et al. The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol, 2012,97(1):14–37

    Article  PubMed  PubMed Central  Google Scholar 

  9. Prunell GF, Svendgaard NA, Alkass K, et al. Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain. J Neurosurg, 2005,102(6):1046–1054

    Article  PubMed  Google Scholar 

  10. Asher E, Payne CM, Bernstein C. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis, light microscopy and electron microscopy. II. Induction of non-classic apoptosis (“para-apoptosis”) by tritiated thymidine. Leuk Lymphoma, 1995,19(1-2):107–119

    CAS  PubMed  Google Scholar 

  11. Caner B, Hou J, Altay O, et al. Transition of research focus from vasospasm to early brain injury after subarachnoid hemorrhage. J Neurochem, 2012;2:12–21

    Article  Google Scholar 

  12. Yuksel S, Tosun YB, Cahill J, et al. Early brain injury following aneurysmal subarachnoid hemorrhage: emphasis on cellular apoptosis. Turk Neurosurg, 2012,22(5):529–533

    PubMed  Google Scholar 

  13. Wang G, Liu K, Li Y, et al. Endoplasmic reticulum stress mediates the anti-inflammatory effect of ethyl pyruvate in endothelial cells. PLoS One. 2014, 9(12):e113983

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lee AS. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci, 2001,26(8):504–510

    Article  CAS  PubMed  Google Scholar 

  15. Thon M, Hosoi T, Yoshii M, et al. Leptin induced GRP78 expression through the PI3K-mTOR pathway in neuronal cells. Sci Rep, 2014,4:7096

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hyoda K, Hosoi T, Horie N, et al. Pi3k-Akt inactivation induced chop expression in endoplasmic reticulumstressed cells. Biochem Biophys Res Commun, 2006, 340(1):286–290

    Article  CAS  PubMed  Google Scholar 

  17. Nakagawa T, Zhu H, Morishima N, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-Beta. Nature, 2000,403(6765): 98–103

    Article  CAS  PubMed  Google Scholar 

  18. Aragon T, van Anken E, Pincus D, et al. Messenger RNA targeting to endoplasmic reticulum stress signalling sites. Nature, 2009,57(7230):736–740

    Article  Google Scholar 

  19. Chen Y, Wang JJ, Li J, et al. Activating transcription factor 4 mediates hyperglycaemia-induced endothelial inflammation and retinal vascular leakage through activation of STAT3 in a mouse model of type 1 diabetes. Diab, 2012,55(9):2533–2545

    Article  CAS  Google Scholar 

  20. Esfandiari F, Medici V, Wong DH, et al. Epigenetic regulation of hepatic endoplasmic reticulum stress pathways in the ethanol-fed cystathionine beta synthase-deficient mouse. Hepatology,2010 51(3):932–941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Ting Lei  (雷 霆).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81360185) and the Foundation of the First Affiliated Hospital of Medical College of Shihezi University of China (No. SS2011-095).

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Liu, Q., Zhao, D., Ji, YX. et al. Role of glucose-regulated protein 78 in early brain injury after experimental subarachnoid hemorrhage in rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 168–173 (2016). https://doi.org/10.1007/s11596-016-1561-3

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  • DOI: https://doi.org/10.1007/s11596-016-1561-3

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