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

Autor:	Hamed Zaer, Wei Fan, Dariusz Orlowski, Andreas N. Glud, Morten B. Jensen, Esben S. Worm, Slávka Lukacova, Trine W. Mikkelsen, Lise M. Fitting, Liisa M. Jacobsen, Thomas Portmann, Jui-Yi Hsieh, Christopher Noel, Georg Weidlich, Woody Chung, Patrick Riley, Cesare Jenkins, John R. Adler, M. Bret Schneider, Jens Christian H. Sørensen, Albrecht Stroh
Jazyk:	angličtina
Rok vydání:	2022
Předmět:	Swine Neuromodulation Spontaneous firing rate Visual evoked potential Stereotactic radiosurgery Visual cortex Minipig General Neuroscience Biophysics Brain Radiosurgery Radiation Ionizing Animals Evoked Potentials Visual Swine Miniature Neurology (clinical)
Zdroj:	Zaer, H, Fan, W, Orlowski, D, Glud, A N, Jensen, M B, Worm, E S, Lukacova, S, Mikkelsen, T W, Fitting, L M, Jacobsen, L M, Portmann, T, Hsieh, J Y, Noel, C, Weidlich, G, Chung, W, Riley, P, Jenkins, C, Adler, J R, Schneider, M B, Sørensen, J C H & Stroh, A 2022, ' Non-ablative doses of focal ionizing radiation alters function of central neural circuits ', Brain Stimulation, vol. 15, no. 3, pp. 586-597 . https://doi.org/10.1016/j.brs.2022.04.001 Brain stimulation, 15(3):586-597
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86df08cc8d5ac09065d2d40131fc6be0 https://pure.au.dk/portal/da/publications/nonablative-doses-of-focal-ionizing-radiation-alters-function-of-central-neural-circuits(c5e8d28d-f6ee-4e2e-b4cd-aaa663240b44).html Zobrazit plný text záznamu