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.
Highlights
Stereotactic radiosurgery (SRS) using gamma radiation is currently used to treat trigeminal neuralgia, primary brain tumors and metastases [1,2] and is being explored as a treatment for severe depression, obsessive-compulsive disorder (OCD), movement disorders as well as for other refractory psychiatric and central nervous system (CNS) pathologies
CA1 pyramidal neurons are controlled by several forms of GABA-mediated inhibiton that limit discharge activity to only a few milliseconds (GABAA fast) or for several hundred milliseconds (GABAA slow), or control the overall excitability of CA1 neurons (GABAA tonic receptors) [2526]
Paired pulse inhibition of the second Population spike (PS) at 100 ms intervals provides a measure of GABAA slow inhibition (Figure 2)
Summary
Stereotactic radiosurgery (SRS) using gamma radiation is currently used to treat trigeminal neuralgia, primary brain tumors and metastases [1,2] and is being explored as a treatment for severe depression, obsessive-compulsive disorder (OCD), movement disorders as well as for other refractory psychiatric and central nervous system (CNS) pathologies. There have been a number of studies published on how the brain responds to radiosurgery levels of radiation, yet the results have had a mixture of conclusions and the neuronal effects of irradiation remain unclear. Some in vivo and in vitro studies suggest high dose SRS can cause neurotoxicity. Previous studies have demonstrated that neuronal degeneration can occur at 70 to 200 Gy and, at the higher doses (150 and 200 Gy), animals showed histological signs of necrosis, edema, and vessel wall thickening [3]. The same study, which exposed the animal’s right frontal
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