Non-ablative doses of focal ionizing radiation alters function of central neural circuits

  1. Zaer, Hamed
  2. Fan, Wei
  3. Orlowski, Dariusz
  4. Glud, Andreas N.
  5. Jensen, Morten B.
  6. Worm, Esben S.
  7. Lukacova, Slavka
  8. Mikkelsen, Trine W.
  9. Fitting, Lise M.
  10. Jacobsen, Liisa M.
  11. Portmann, Thomas
  12. Hsieh, Jui-Yi
  13. Noel, Christopher
  14. Weidlich, Georg
  15. Chung, Woody
  16. Riley, Patrick
  17. Jenkins, Cesare
  18. Adler, John R., Jr.
  19. Schneider, M. Bret
  20. Sørensen, Jens Christian H.
  21. Stroh, Albrecht

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WeightNameValue
1000 Titel
  • Non-ablative doses of focal ionizing radiation alters function of central neural circuits
1000 Autor/in
  1. Zaer, Hamed |
  2. Fan, Wei |
  3. Orlowski, Dariusz |
  4. Glud, Andreas N. |
  5. Jensen, Morten B. |
  6. Worm, Esben S. |
  7. Lukacova, Slavka |
  8. Mikkelsen, Trine W. |
  9. Fitting, Lise M. |
  10. Jacobsen, Liisa M. |
  11. Portmann, Thomas |
  12. Hsieh, Jui-Yi |
  13. Noel, Christopher |
  14. Weidlich, Georg |
  15. Chung, Woody |
  16. Riley, Patrick |
  17. Jenkins, Cesare |
  18. Adler, John R., Jr. |
  19. Schneider, M. Bret |
  20. Sørensen, Jens Christian H. |
  21. Stroh, Albrecht |
1000 Erscheinungsjahr 2022
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-04-05
1000 Erschienen in
1000 Quellenangabe
  • 15(3):586-597
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1016/j.brs.2022.04.001 |
1000 Ergänzendes Material
  • https://www.brainstimjrnl.com/article/S1935-861X(22)00061-4/fulltext#supplementaryMaterial |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: Modulation of pathological neural circuit activity in the brain with a minimum of complications is an area of intense interest. OBJECTIVE: The goal of the study was to alter neurons' physiological states without apparent damage of cellular integrity using stereotactic radiosurgery (SRS). METHODS: We treated a 7.5 mm-diameter target on the visual cortex of Göttingen minipigs with doses of 40, 60, 80, and 100 Gy. Six months post-irradiation, the pigs were implanted with a 9 mm-wide, eight-shank multi-electrode probe, which spanned the radiation focus as well as the low-exposure neighboring areas. RESULTS: Doses of 40 Gy led to an increase of spontaneous firing rate, six months post-irradiation, while doses of 60 Gy and greater were associated with a decrease. Subjecting the animals to visual stimuli resulted in typical visual evoked potentials (VEP). At 40 Gy, a significant reduction of the P1 peak time, indicative of higher network excitability was observed. At 80 Gy, P1 peak time was not affected, while a minor reduction at 60 Gy was seen. No distance-dependent effects on spontaneous firing rate, or on VEP were observed. Post-mortem histology revealed no evidence of necrosis at doses below 60 Gy. In an in vitro assay comprising of iPS-derived human neuron-astrocyte co-cultures, we found a higher vulnerability of inhibitory neurons than excitatory neurons with respect to radiation, which might provide the cellular mechanism of the disinhibitory effect observed in vivo. CONCLUSION: We provide initial evidence for a rather circuit-wide, long-lasting disinhibitory effect of low sub-ablative doses of SRS.
1000 Sacherschließung
lokal Neuromodulation
lokal Spontaneous firing rate
lokal Visual evoked potential
lokal Stereotactic radiosurgery
lokal Visual cortex
lokal Minipig
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. Boehringer Ingelheim Stiftung |
  2. Deutsche Forschungsgemeinschaft |
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  2. -
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    1000 Förderer Boehringer Ingelheim Stiftung |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer -
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1000 Erstellt am 2023-03-07T08:04:00.396+0100
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