Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival
Abstract Background Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the in...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Bioelectronic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42234-022-00092-0 |
| _version_ | 1828787794407849984 |
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| author | Rishabh C. Choudhary Umair Ahmed Muhammad Shoaib Eric Alper Abdul Rehman Junhwan Kim Koichiro Shinozaki Bruce T. Volpe Sangeeta Chavan Stavros Zanos Kevin J. Tracey Lance B. Becker |
| author_facet | Rishabh C. Choudhary Umair Ahmed Muhammad Shoaib Eric Alper Abdul Rehman Junhwan Kim Koichiro Shinozaki Bruce T. Volpe Sangeeta Chavan Stavros Zanos Kevin J. Tracey Lance B. Becker |
| author_sort | Rishabh C. Choudhary |
| collection | DOAJ |
| description | Abstract Background Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation. Methods Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal’s heart rate and determined a 15–20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively). Results In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group. Conclusions Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery. |
| first_indexed | 2024-12-12T00:39:22Z |
| format | Article |
| id | doaj.art-d4a9a43bf11f4d4fb295592752645278 |
| institution | Directory Open Access Journal |
| issn | 2332-8886 |
| language | English |
| last_indexed | 2024-12-12T00:39:22Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Bioelectronic Medicine |
| spelling | doaj.art-d4a9a43bf11f4d4fb2955927526452782022-12-22T00:44:18ZengBMCBioelectronic Medicine2332-88862022-07-018111210.1186/s42234-022-00092-0Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survivalRishabh C. Choudhary0Umair Ahmed1Muhammad Shoaib2Eric Alper3Abdul Rehman4Junhwan Kim5Koichiro Shinozaki6Bruce T. Volpe7Sangeeta Chavan8Stavros Zanos9Kevin J. Tracey10Lance B. Becker11Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical ResearchLaboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthDonald and Barbara Zucker School of Medicine at Hofstra/NorthwellLaboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthLaboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthLaboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthZucker School of Medicine at Hofstra/NorthwellInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical ResearchInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical ResearchInstitute of Bioelectronic Medicine, Feinstein Institutes for Medical ResearchLaboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell HealthAbstract Background Vagus nerve stimulation (VNS) has shown therapeutic potential in a variety of different diseases with many ongoing clinical trials. The role of VNS in reducing ischemic injury in the brain requires further evaluation. Cardiac arrest (CA) causes global ischemia and leads to the injury of vital organs, especially the brain. In this study, we investigated the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation. Methods Sprague-Dawley rats underwent 12 min asphyxia-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve. To optimize a threshold, we used animal’s heart rate and determined a 15–20% drop from baseline levels as the effective and physiological threshold for each animal. The primary endpoint was 72 h survival; secondary endpoints included neurological functional recovery, reduction in brain cellular injury (histopathology), cardiac and renal injury parameters (troponin I and creatinine levels, respectively). Results In comparison to the control group, tVNS significantly improved 72 h survival and brain functional recovery after 12 minutes of CA. The tVNS group demonstrated significantly reduced numbers of damaged neurons in the CA1 hippocampal region of the brain as compared to the control group. Similarly, the tVNS group showed decreased trend in plasma troponin I and creatinine levels as compared to the control group. Conclusions Our findings suggest that using tVNS for 2 h after 12 minutes of CA attenuates ischemia neuronal cell death, heart and kidney damage, and improves 72 h survival with improved neurological recovery.https://doi.org/10.1186/s42234-022-00092-0Cardiac arrestVagus nerve stimulationIschemia-reperfusion injuryNeuroprotection |
| spellingShingle | Rishabh C. Choudhary Umair Ahmed Muhammad Shoaib Eric Alper Abdul Rehman Junhwan Kim Koichiro Shinozaki Bruce T. Volpe Sangeeta Chavan Stavros Zanos Kevin J. Tracey Lance B. Becker Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival Bioelectronic Medicine Cardiac arrest Vagus nerve stimulation Ischemia-reperfusion injury Neuroprotection |
| title | Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| title_full | Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| title_fullStr | Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| title_full_unstemmed | Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| title_short | Threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| title_sort | threshold adjusted vagus nerve stimulation after asphyxial cardiac arrest results in neuroprotection and improved survival |
| topic | Cardiac arrest Vagus nerve stimulation Ischemia-reperfusion injury Neuroprotection |
| url | https://doi.org/10.1186/s42234-022-00092-0 |
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