Skip to main content

Advertisement

Log in

Effect of Electrical Vagus Nerve Stimulation on Cerebral Blood Flow and Neurological Outcome in Asphyxial Cardiac Arrest Model of Rats

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

Vagus nerve stimulation (VNS) during post-resuscitation may increase recovery of cerebral blood flow (CBF) and reduce neurological injury.

Objective

This study was designed to investigate the effect of electrical VNS on neurological outcomes following cardiac arrest (CA).

Methods

Male Sprague–Dawley rats (n = 48) were subjected to the asphyxial CA model and blindly allocated to the VN isolation (CA + VN isolation) or VNS group (CA + VNS group). Cardiopulmonary resuscitation was initiated 450 s after pulseless electrical arrest, and the left cervical vagus nerve was electrically stimulated (0.05 mA, 1 Hz) for 3 h in the CA + VNS group. The neurological deficit score (NDS) and overall performance category (OPC) were assessed at 24 h after resuscitation, and histological injury of the hippocampus was evaluated. Independent experiments were performed to evaluate the effect of VNS on global cortical CBF after resuscitation using laser speckle Doppler imaging through a thinned skull window from pre-arrest to 6 h after resuscitation.

Results

The baseline characteristics were not significantly different between the two groups. The NDS was significantly higher, and the OPC was substantially lower in the CA + VNS group (p = 0.022 and p = 0.049, respectively) supported by decrease in histological injury of the hippocampal CA1 region. CBF in the early period of post-return of spontaneous circulation (ROSC) was significantly higher in the CA + VNS group (p < 0.05 at post-ROSC 2 h and 4 h), and 4-hydroxynonenal was significantly lower in the CA + VNS group (p = 0.026).

Conclusions

VNS improved cerebral perfusion and neurological outcomes at 24 h after ROSC in an asphyxial CA model of rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79(3):350–79.

    Article  PubMed  Google Scholar 

  2. Mangus DB, Huang L, Applegate PM, et al. A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (part I—protection via specific pathways). Med Gas Res. 2014;4:9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Huang L, Applegate PM, Gatling JW, et al. A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (part II—comprehensive protection). Med Gas Res. 2014;4:10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.

    Article  CAS  Google Scholar 

  5. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.

    Article  Google Scholar 

  6. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.

    Article  Google Scholar 

  7. Iordanova B, Li L, Clark RSB, Manole MD. Alterations in cerebral blood flow after resuscitation from cardiac arrest. Front Pediatr. 2017;5:174.

    Article  PubMed  PubMed Central  Google Scholar 

  8. van den Brule JM, Vinke EJ, van Loon LM, van der Hoeven JG, Hoedemaekers CW. Low spontaneous variability in cerebral blood flow velocity in non-survivors after cardiac arrest. Resuscitation. 2017;111:110–5.

    Article  PubMed  Google Scholar 

  9. Chen WL, Tsai TH, Huang CC, Chen JH, Kuo CD. Heart rate variability predicts short-term outcome for successfully resuscitated patients with out-of-hospital cardiac arrest. Resuscitation. 2009;80(10):1114–8.

    Article  PubMed  Google Scholar 

  10. Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405(6785):458–62.

    Article  CAS  PubMed  Google Scholar 

  11. Jiang Y, Li L, Liu B, et al. Vagus nerve stimulation attenuates cerebral ischemia and reperfusion injury via endogenous cholinergic pathway in rat. PLoS ONE. 2014;9(7):e102342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ay I, Nasser R, Simon B, Ay H. Transcutaneous cervical vagus nerve stimulation ameliorates acute ischemic injury in rats. Brain Stimul. 2016;9(2):166–73.

    Article  Google Scholar 

  13. Jiang Y, Li L, Ma J, et al. Auricular vagus nerve stimulation promotes functional recovery and enhances the post-ischemic angiogenic response in an ischemia/reperfusion rat model. Neurochem Int. 2016;97:73–82.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang L, Ma J, Jin X, et al. L-PGDS mediates vagus nerve stimulation-induced neuroprotection in a rat model of ischemic stroke by suppressing the apoptotic response. Neurochem Res. 2017;42(2):644–55.

    Article  CAS  PubMed  Google Scholar 

  15. Sun P, Wang J, Zhao S, et al. Improved outcomes of cardiopulmonary resuscitation in rats treated with vagus nerve stimulation and its potential mechanism. Shock. 2018;49(6):698–703.

    Article  PubMed  Google Scholar 

  16. Zobel A, Joe A, Freymann N, et al. Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Res. 2005;139(3):165–79.

    Article  PubMed  Google Scholar 

  17. Willie CK, Tzeng YC, Fisher JA, Ainslie PN. Integrative regulation of human brain blood flow. J Physiol. 2014;592(5):841–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: National Academies Press; 2011.

    Google Scholar 

  19. Lee JH, Kim K, Jo YH, et al. Effect of valproic acid on survival and neurologic outcomes in an asphyxial cardiac arrest model of rats. Resuscitation. 2013;84(10):1443–9.

    Article  CAS  PubMed  Google Scholar 

  20. Jia X, Koenig MA, Shin HC, et al. Improving neurological outcomes post-cardiac arrest in a rat model: immediate hypothermia and quantitative EEG monitoring. Resuscitation. 2008;76(3):431–42.

    Article  PubMed  Google Scholar 

  21. Winship IR. Laser speckle contrast imaging to measure changes in cerebral blood flow. Methods Mol Biol. 2014;1135:223–35.

    Article  PubMed  Google Scholar 

  22. Buunk G, van der Hoeven JG, Meinders AE. Cerebral blood flow after cardiac arrest. Neth J Med. 2000;57(3):106–12.

    Article  CAS  PubMed  Google Scholar 

  23. He J, Lu H, Young L, et al. Real-time quantitative monitoring of cerebral blood flow by laser speckle contrast imaging after cardiac arrest with targeted temperature management. J Cereb Blood Flow Metab. 2017;2017:271678X17748787.

    Google Scholar 

  24. Manole MD, Kochanek PM, Bayir H, et al. Brain tissue oxygen monitoring identifies cortical hypoxia and thalamic hyperoxia after experimental cardiac arrest in rats. Pediatr Res. 2014;75(2):295–301.

    Article  CAS  PubMed  Google Scholar 

  25. Henry TR, Votaw JR, Pennell PB, et al. Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology. 1999;52(6):1166–73.

    Article  CAS  PubMed  Google Scholar 

  26. Pardo JV, Sheikh SA, Schwindt GC, et al. Chronic vagus nerve stimulation for treatment-resistant depression decreases resting ventromedial prefrontal glucose metabolism. Neuroimage. 2008;42(2):879–89.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rutecki P. Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia. 1990;31(Suppl 2):S1–6.

    Article  PubMed  Google Scholar 

  28. Parada E, Egea J, Buendia I, et al. The microglial alpha7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2. Antioxid Redox Signal. 2013;19(11):1135–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Miyamoto O, Pang J, Sumitani K, et al. Mechanisms of the anti-ischemic effect of vagus nerve stimulation in the gerbil hippocampus. NeuroReport. 2003;14(15):1971–4.

    Article  PubMed  Google Scholar 

  30. Follesa P, Biggio F, Gorini G, et al. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 2007;1179:28–34.

    Article  CAS  PubMed  Google Scholar 

  31. Kim C, Fahrenbruch CE, Cobb LA, Eisenberg MS. Out-of-hospital cardiac arrest in men and women. Circulation. 2001;104(22):2699–703.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the technical assistance of animal care provided by pre-clinical experimental center in SNUBH.

Funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1B03034360).

Author information

Authors and Affiliations

Authors

Contributions

JHL and YHJ designed the study and prepared the protocol. BK, IP, SK, MJL, and JHL performed experiments. All authors participated in interpretation of data. BK, IP, and JHL drafted and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jae Hyuk Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

The Institutional Animal Care and Use Committee of Seoul National University Bundang Hospital (protocol no. BA1705-223/042-01) approved this study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 677 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, B., Park, I., Lee, J.H. et al. Effect of Electrical Vagus Nerve Stimulation on Cerebral Blood Flow and Neurological Outcome in Asphyxial Cardiac Arrest Model of Rats. Neurocrit Care 30, 572–580 (2019). https://doi.org/10.1007/s12028-018-0640-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-018-0640-7

Keywords

Navigation