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Original article
peer-reviewed

High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition



Abstract

Studies on the effects of gamma radiation on brain tissue have produced markedly differing results, ranging from little effect to major pathology, following irradiation. The present study used control-matched animals to compare effects on a well characterized brain region following gamma irradiation. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24-hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and measured for anatomical and physiological differences. There were no major changes observed in tissue appearance or evoked synaptic responses at any post-irradiation time point. However, exposure to 60 Gy of irradiation resulted in a small, but statistically significant (14% change; ANOVA p < 0.005; n = 9) reduction in synaptic inhibition seen at 100 ms, indicating a selective depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition. Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n = 9) when comparing the 24-hour group to sham group. Effects on PS amplitude recovered to baseline 48 hour and one week later. There were no obvious negative pathological effects; however, a subtle depression in circuit level inhibition was observed and provides evidence for ‘radiomodulation’ of brain circuits.



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Original article
peer-reviewed

High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition


Author Information

Beza A. Dagne

Anesthesia, Stanford University School of Medicine

Melis K. Sunay

Anesthesia, Stanford University School of Medicine

Noëlie S. Cayla

Anesthesia, Stanford University School of Medicine

Yi-Bing Ouyang

Anesthesia, Stanford University School of Medicine

Susan J. Knox

Department of Radiation Oncology, Stanford University Medical Center

Rona G. Giffard

Anesthesia, Stanford University School of Medicine

John R. Adler

Department of Neurosurgery, Stanford University School of Medicine

Department of Radiation Oncology, Stanford University Medical Center

Bruce Maciver Corresponding Author

Anesthesia, Stanford University School of Medicine


Ethics Statement and Conflict of Interest Disclosures

Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All experiments described herein were pre-approved by the Stanford University Administrative Panel for Laboratory Animal Care. Procedures were in accordance to National Institute of Health guidelines and procedures approved by Stanford University’s Institutional Animal Care Committee. Issued protocol number 13385. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Work was funded in part by a grant from Varian Medical Systems. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Acknowledgements

This research was partially supported by a corporate gift from Varian Medical Sytems.


Original article
peer-reviewed

High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition


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Original article
peer-reviewed

High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition

Beza A. Dagne">Beza A. Dagne, Melis K. Sunay">Melis K. Sunay, Noëlie S. Cayla">Noëlie S. Cayla, Yi-Bing Ouyang">Yi-Bing Ouyang, Susan J. Knox">Susan J. Knox, Rona G. Giffard">Rona G. Giffard, John R. Adler">John R. Adler, Bruce Maciver">Bruce Maciver

  • Author Information
    Beza A. Dagne

    Anesthesia, Stanford University School of Medicine

    Melis K. Sunay

    Anesthesia, Stanford University School of Medicine

    Noëlie S. Cayla

    Anesthesia, Stanford University School of Medicine

    Yi-Bing Ouyang

    Anesthesia, Stanford University School of Medicine

    Susan J. Knox

    Department of Radiation Oncology, Stanford University Medical Center

    Rona G. Giffard

    Anesthesia, Stanford University School of Medicine

    John R. Adler

    Department of Neurosurgery, Stanford University School of Medicine

    Department of Radiation Oncology, Stanford University Medical Center

    Bruce Maciver Corresponding Author

    Anesthesia, Stanford University School of Medicine


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All experiments described herein were pre-approved by the Stanford University Administrative Panel for Laboratory Animal Care. Procedures were in accordance to National Institute of Health guidelines and procedures approved by Stanford University’s Institutional Animal Care Committee. Issued protocol number 13385. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Work was funded in part by a grant from Varian Medical Systems. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements

    This research was partially supported by a corporate gift from Varian Medical Sytems.


    Article Information

    Published: March 04, 2017

    DOI

    10.7759/cureus.1076

    Cite this article as:

    Dagne B A, Sunay M K, Cayla N S, et al. (March 04, 2017) High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition. Cureus 9(3): e1076. doi:10.7759/cureus.1076

    Publication history

    Received by Cureus: December 20, 2016
    Peer review began: January 21, 2017
    Peer review concluded: February 22, 2017
    Published: March 04, 2017

    Copyright

    © Copyright 2017
    Dagne et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Studies on the effects of gamma radiation on brain tissue have produced markedly differing results, ranging from little effect to major pathology, following irradiation. The present study used control-matched animals to compare effects on a well characterized brain region following gamma irradiation. Male Sprague-Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24-hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and measured for anatomical and physiological differences. There were no major changes observed in tissue appearance or evoked synaptic responses at any post-irradiation time point. However, exposure to 60 Gy of irradiation resulted in a small, but statistically significant (14% change; ANOVA p < 0.005; n = 9) reduction in synaptic inhibition seen at 100 ms, indicating a selective depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition. Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n = 9) when comparing the 24-hour group to sham group. Effects on PS amplitude recovered to baseline 48 hour and one week later. There were no obvious negative pathological effects; however, a subtle depression in circuit level inhibition was observed and provides evidence for ‘radiomodulation’ of brain circuits.



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Beza A. Dagne

Anesthesia, Stanford University School of Medicine

Melis K. Sunay

Anesthesia, Stanford University School of Medicine

Noëlie S. Cayla

Anesthesia, Stanford University School of Medicine

Yi-Bing Ouyang

Anesthesia, Stanford University School of Medicine

Susan J. Knox

Department of Radiation Oncology, Stanford University Medical Center

Rona G. Giffard

Anesthesia, Stanford University School of Medicine

John R. Adler, M.D.

Department of Neurosurgery, Stanford University School of Medicine

Bruce Maciver, Ph.D., M.Sc., Professor

Anesthesia, Stanford University School of Medicine

For correspondence:
maciver@stanford.edu

Beza A. Dagne

Anesthesia, Stanford University School of Medicine

Melis K. Sunay

Anesthesia, Stanford University School of Medicine

Noëlie S. Cayla

Anesthesia, Stanford University School of Medicine

Yi-Bing Ouyang

Anesthesia, Stanford University School of Medicine

Susan J. Knox

Department of Radiation Oncology, Stanford University Medical Center

Rona G. Giffard

Anesthesia, Stanford University School of Medicine

John R. Adler, M.D.

Department of Neurosurgery, Stanford University School of Medicine

Bruce Maciver, Ph.D., M.Sc., Professor

Anesthesia, Stanford University School of Medicine

For correspondence:
maciver@stanford.edu