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Neurocritical Care

, Volume 30, Issue 1, pp 98–105 | Cite as

Hyperbaric Oxygen Protects Against Cerebral Damage in Permanent Middle Cerebral Artery Occlusion Rats and Inhibits Autophagy Activity

  • KongMiao Lu
  • HaiRong Wang
  • XiaoLi Ge
  • QingHua Liu
  • Miao Chen
  • Yong Shen
  • Xuan Liu
  • ShuMing PanEmail author
Original Article

Abstract

Background

To investigate the effects of hyperbaric oxygen (HBO) on brain damage and autophagy levels in a rat model of middle cerebral artery occlusion.

Methods

Neurologic injury and infarcted areas were evaluated according to the modified neurological severity score and 2,3,5-triphenyltetrazolium chloride staining. Western blots were used to determine beclin1, caspase-3 and fodrin1 protein expression. Beclin1 protein expression (an autophagy marker), positive terminal dUTP nick-end labeling (TUNEL) staining (an apoptosis marker) and positive propidium iodide (PI) staining (a necrosis marker) were detected by immunofluorescence.

Results

Our results indicated that HBO could decrease the infarct volume and speed up the recovery of the neurological deficit scores in ischemic rats. Beclin1 was down-regulated after HBO treatment. HBO treatment inhibited fodrin1 protein expression and decreased the number of PI-positive cells. HBO also down-regulated caspase-3 and decreased the number of TUNEL-positive cells.

Conclusion

Cerebral ischemia caused early neuronal death due to necrosis, followed by delayed neuronal death due to apoptosis. Consequently, autophagy might be involved in all processes of ischemia. HBO could protect the brain against ischemic injury, and the possible mechanisms might be correlated with decreased autophagy activity and decreased apoptosis and necrosis levels.

Keywords

Hyperbaric oxygen Cerebral infarction Autophagy Apoptosis Necrosis 

Notes

Author Contributions

KML participated in study design, collection of data, analysis of data, interpretation of results, drafted, and finalized the manuscript. HRW participated in study design, interpretation of results and reviewed. XLG participated in study design and interpretation of the results. QHL participated in study design and interpretation of the results. MC participated in study design, interpretation of the results. YS participated in collection of data, analysis of data and interpretation of results. XL participated in collection of data, analysis of data and interpretation of results. SMP participated in initiation of the study, study design, drafted, and finalized the manuscript.

Source of Support

Funding was provided by National Key Clinical Medicine Construction Program on Emergency Department; Emergency Medicine-Hospital Supported Key Department Program in 2013; Public Health Talent Training Plan of Shanghai, GWDTR201219; post the outstanding young medical talent plan of Xinhua hospital; the Doctorial Innovation Fund of Shanghai Jiao Tong University School of Medicine (BXJ201726).

Compliance with Ethical Standards

Conflict of interest

All authors disclose that they have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) this work. This includes employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.

Supplementary material

12028_2018_577_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1785 kb)

References

  1. 1.
    Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008;371(9624):1612–23.CrossRefGoogle Scholar
  2. 2.
    Cheng Y, Deshmukh M, D’Costa A, Demaro JA, Gidday JM, Shah A, et al. Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury. J Clin Investig. 1998;101(9):1992–9.CrossRefGoogle Scholar
  3. 3.
    Gill R, Soriano M, Blomgren K, Hagberg H, Wybrecht R, Miss MT, et al. Role of caspase-3 activation in cerebral ischemia-induced neurodegeneration in adult and neonatal brain. J Cereb Blood Flow Metab. 2002;22(4):420–30.CrossRefGoogle Scholar
  4. 4.
    Joly LM, Mucignat V, Mariani J, Plotkine M, Charriaut-Marlangue C. Caspase inhibition after neonatal ischemia in the rat brain. J Cereb Blood Flow Metab. 2004;24(1):124–31.CrossRefGoogle Scholar
  5. 5.
    Renolleau S, Fau S, Goyenvalle C, Joly LM, Chauvier D, Jacotot E, et al. Specific caspase inhibitor Q-VD-OPh prevents neonatal stroke in P7 rat: a role for gender. J Neurochem. 2007;100(4):1062–71.CrossRefGoogle Scholar
  6. 6.
    Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000;290(5497):1717–21.CrossRefGoogle Scholar
  7. 7.
    Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–52.CrossRefGoogle Scholar
  8. 8.
    Yang Z, Klionsky DJ. Eaten alive: a history of macroautophagy. Nat Cell Biol. 2010;12(9):814–22.CrossRefGoogle Scholar
  9. 9.
    Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science. 2004;306(5698):990–5.CrossRefGoogle Scholar
  10. 10.
    Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2001;2(4):330–5.CrossRefGoogle Scholar
  11. 11.
    Matchett GA, Martin RD, Zhang JH. Hyperbaric oxygen therapy and cerebral ischemia: neuroprotective mechanisms. Neurol Res. 2009;31(2):114–21.CrossRefGoogle Scholar
  12. 12.
    Nemoto EM, Betterman K. Basic physiology of hyperbaric oxygen in brain. Neurol Res. 2007;29(2):116–26.CrossRefGoogle Scholar
  13. 13.
    Yin X, Meng F, Wang Y, Wei W, Li A, Chai Y, et al. Effect of hyperbaric oxygen on neurological recovery of neonatal rats following hypoxic-ischemic brain damage and its underlying mechanism. Int J Clin Exp Pathol. 2013;6(1):66–75.Google Scholar
  14. 14.
    Lin KC, Niu KC, Tsai KJ, Kuo JR, Wang LC, Chio CC, et al. Attenuating inflammation but stimulating both angiogenesis and neurogenesis using hyperbaric oxygen in rats with traumatic brain injury. J Trauma Acute Care Surg. 2012;72(3):650–9.CrossRefGoogle Scholar
  15. 15.
    Wang XL, Yang YJ, Xie M, Yu XH, Liu CT, Wang X. Proliferation of neural stem cells correlates with Wnt-3 protein in hypoxic-ischemic neonate rats after hyperbaric oxygen therapy. NeuroReport. 2007;18(16):1753–6.CrossRefGoogle Scholar
  16. 16.
    Yan W, Zhang H, Bai X, Lu Y, Dong H, Xiong L. Autophagy activation is involved in neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats. Brain Res. 2011;1402:109–21.CrossRefGoogle Scholar
  17. 17.
    Lu Y, Kang J, Bai Y, Zhang Y, Li H, Yang X, et al. Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation. Eur J Pharmacol. 2014;728:93–9.CrossRefGoogle Scholar
  18. 18.
    Rupadevi M, Parasuraman S, Raveendran R. Protocol for middle cerebral artery occlusion by an intraluminal suture method. J Pharmacol Pharmacother. 2011;2(1):36–9.CrossRefGoogle Scholar
  19. 19.
    Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001;32(11):2682–8.CrossRefGoogle Scholar
  20. 20.
    Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000;20(9):1311–9.CrossRefGoogle Scholar
  21. 21.
    Ashwal S, Tone B, Tian HR, Cole DJ, Pearce WJ. Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke. 1998;29(5):1037–46.CrossRefGoogle Scholar
  22. 22.
    Saatman KE, Creed J, Raghupathi R. Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics. 2010;7(1):31–42.CrossRefGoogle Scholar
  23. 23.
    Saido TC, Yokota M, Nagao S, Yamaura I, Tani E, Tsuchiya T, et al. Spatial resolution of fodrin proteolysis in postischemic brain. J Biol Chem. 1993;268(33):25239–43.Google Scholar
  24. 24.
    Northington FJ, Zelaya ME, O’Riordan DP, Blomgren K, Flock DL, Hagberg H, et al. Failure to complete apoptosis following neonatal hypoxia–ischemia manifests as ‘‘continuum” phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain. Neuroscience. 2007;149(4):822–33.CrossRefGoogle Scholar
  25. 25.
    Puyal J, Vaslin A, Mottier V, Clarke PG. Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann Neurol. 2009;66(3):378–89.CrossRefGoogle Scholar
  26. 26.
    Hossmann KA. Viability thresholds and the penumbra of focal ischemia. Ann Neurol. 1994;36(4):557–65.CrossRefGoogle Scholar
  27. 27.
    Northington FJ, Ferriero DM, Graham EM, Traystman RJ, Martin LJ. Early neurodegeneration after hypoxia–ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis. Neurobiol Dis. 2001;8(2):207–19.CrossRefGoogle Scholar
  28. 28.
    Benjelloun N, Joly LM, Palmier B, Plotkine M, Charriaut-Marlangue C. Apoptotic mitochondrial pathway in neurones and astrocytes after neonatal hypoxia–ischaemia in the rat brain. Neuropathol Appl Neurobiol. 2003;29(4):350–60.CrossRefGoogle Scholar
  29. 29.
    Edinger AL, Thompson CB. Defective autophagy leads to cancer. Cancer Cell. 2003;4:422–4.CrossRefGoogle Scholar
  30. 30.
    Rockswold SB, Rockswold GL, Defillo A. Hyperbaric oxygen in traumatic brain injury. Neurol Res. 2007;29(2):162–72.CrossRefGoogle Scholar
  31. 31.
    Bao DS, Wu YK, Fu SJ, Wang GY, Yang SJ, Liang GB, et al. Hyperbaric oxygenation protects against ischemia-reperfusion injury in transplanted rat kidneys by triggering autophagy and inhibiting inflammatory response. Ann Transplant. 2017;10(22):75–82.CrossRefGoogle Scholar
  32. 32.
    Sun Y, Liu D, Su P, Lin F, Tang Q. Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy. Neurosci Lett. 2016;618:139–45.CrossRefGoogle Scholar
  33. 33.
    Chen C, Chen W, Li Y, Dong Y, Teng X, Nong Z, et al. Hyperbaric oxygen protects against myocardial reperfusion injury via the inhibition of inflammation and the modulation of autophagy. Oncotarget. 2017;8(67):111522–34.Google Scholar
  34. 34.
    Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, et al. Cerebral ischemia hypoxia induces intravascular coagulation and autophagy. Am J Pathol. 2006;169(2):566–83.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2018

Authors and Affiliations

  1. 1.Department of Emergency, Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.General ICU, Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

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