Search

The biological effects and regulatory mechanisms of low-dose and low-dose-rate radiation are still rather controversial. Therefore, in this study we investigated the effects of low-dose-rate radiation on zebrafish neurodevelopment and the role of miRNAs in radiation-induced neurodevelopment. Zebrafish embryos received prolonged gamma-ray irradiation (0 mGy/h, 0.1 mGy/h, 0.2 mGy/h, 0.4 mGy/h) during development. Neurodevelopmental indicators included mortality, malformation rate, swimming speed, as well as the morphology changes of the lateral line system and brain tissue. Additionally, spatiotemporal expression of development-related miRNAs (dre-miR-196a-5p, dre-miR-210-3p, dre-miR-338) and miRNA processing enzymes genes (Dicer and Drosha) were assessed by qRT-PCR and whole mount in situ hybridization (WISH). The results revealed a decline in mortality, malformation and swimming speed, with normal histological and morphological appearance, in zebrafish that received 0.1 mGy/h; however, increased mortality, malformation and swimming speed were observed, with pathological changes, in zebrafish that received 0.2 mGy/h and 0.4 mGy/h. The expression of miRNA processing enzyme genes was altered after irradiation, and miRNAs expression was downregulated in the 0.1 mGy/h group, and upregulated in the 0.2 mGy/h and 0.4 mGy/h groups. Furthermore, ectopic expression of dre-miR-210-3p, Dicer and Drosha was also observed in the 0.4 mGy/h group. In conclusion, the effect of low-dose and low-dose-rate radiation on neurodevelopment follows the threshold model, under the regulation of miRNAs, excitatory effects occurred at a dose rate of 0.1 mGy/h and toxic effects occurred at a dose rate of 0.2 mGy/h and 0.4 mGy/h., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Low-intensity, low-frequency ultrasound (LILFU) has recently emerged as a promising technique to modulate non-invasively nerve activities at lower cost than other traditional and more-invasive neuromodulation methods. However, there is currently no consensus on the optimum sonication parameters to be used in LILFU applications, and most of the accepted ranges have arisen from trial-and-error approaches. Here we utilise a recently proposed micromechanics model of membrane flexoelectricity, a potential candidate for neuromodulation, and simulate action potentials/membrane polarisation triggered by acoustic pulses of different pulse frequencies, pulse magnitudes and duty cycles. Results reveal that, at constant duty cycles, increasing the transmit frequency increases the thresholds of both the pulse magnitude and the elastic energy rate density required to mechanically trigger an action potential, whereas at constant frequencies, increasing the duty cycle reduces both. The influence of transmit frequency is weakened at lower duty cycles. Our simulation results offer some guidance on the selections of sonication parameters used in LILFU for neurologic disorder treatments in the context of the flexoelectricity hypothesis., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Regulator of G-protein signaling 7 (RGS7) is predominately present in the nervous system and is essential for neuronal signaling involving G-proteins. Prior studies in cultured cells showed that RGS7 is regulated via proteasomal degradation, however no protein is known to facilitate proteasomal degradation of RGS7 and it has not been shown whether this regulation affects G-protein signaling in neurons. Here we used a knockout mouse model with conditional deletion of arginyltransferase (Ate1) in the nervous system and found that in retinal ON bipolar cells, where RGS7 modulates a G-protein to signal light increments, deletion of Ate1 raised the level of RGS7. Electroretinographs revealed that lack of Ate1 leads to increased light-evoked response sensitivities of ON-bipolar cells, as well as their downstream neurons. In cultured mouse embryonic fibroblasts (MEF), RGS7 was rapidly degraded via proteasome pathway and this degradation was abolished in Ate1 knockout MEF. Our results indicate that Ate1 regulates RGS7 protein level by facilitating proteasomal degradation of RGS7 and thus affects G-protein signaling in neurons.

Background: Nerves are key factors in prostate cancer (PCa) progression. Here, we propose that neuropeptide Y (NPY) nerves are key regulators of cancer-nerve interaction., Methods: We used in vitro models for NPY inhibition studies and subsequent metabolomics, apoptotic and migration assays, and nuclear transcription factor-κB (NF-κB) translocation studies. Human naïve and radiated PCa tissues were used for NPY nerve density biomarker studies. Tissues derived from a Botox denervation clinical trial were used to corroborate metabolomic changes in humans., Results: Cancer cells increase NPY positive nerves in vitro and in preneoplastic human tissues. NPY-specific inhibition resulted in increased cancer apoptosis, decreased motility, and energetic metabolic pathway changes. A comparison of metabolomic response in NPY-inhibited cells with the transcriptome response in human PCa patients treated with Botox showed shared 13 pathways, including the tricarboxylic acid cycle. We identified that NF-κB is a potential NPY downstream mediator. Using in vitro models and tissues derived from a previous human chemical denervation study, we show that Botox specifically, but not exclusively, inhibits NPY in cancer. Quantification of NPY nerves is independently predictive of PCa-specific death. Finally, NPY nerves might be involved in radiation therapy (RT) resistance, as radiation-induced apoptosis is reduced when PCa cells are cocultured with dorsal root ganglia/nerves and NPY positive nerves are increased in prostates of patients that failed RT., Conclusion: These data suggest that targeting the NPY neural microenvironment may represent a therapeutic approach for the treatment of PCa and resistance through the regulation of multiple oncogenic mechanisms., (© 2020 The Authors. The Prostate published by Wiley Periodicals LLC.)

The review analyzes the change of the existing paradigm of high radioresistance of the nervous system according tothe results of the study of neuropsychiatric disorders in in the aftermath of the Chornobyl accident in both earlyand remote post-accident period. The participation of the endocannabinoid system in ensuring homeostasis andpathology formation, potential possibilities of using cannabis drugs, agonists and antagonists of endocannabinoidreceptors for the treatment of early and long-term effects of radiation are considered., (H. V. Kosiakova, S. А. Chumak, A. G. Berdyshev, I. Ya. Pinchuk, N. M. Hula, А. А. Chumak.)

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection., Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment., Data Sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018., Study Eligibility Criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions., Study Appraisal and Synthesis Methods: Studies were evaluated using the Cochrane Collaboration's risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed., Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout. There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found., Limitations, Conclusions, and Implications of Key Findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence., Systematic Review Registration Number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902)., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.

Objective: to study the state of cognitive functions in children who were born and permanently live at radioactive contaminated territories (RCT) with pathology of the upper digestive tract, using pathopsychological testing; to increase the effectiveness of treatment and prophylactic measures aimed at preserving and restoring the health of RCT residents., Design, Patients and Methods: A randomized blind controlled clinical trial was conducted. There were examined, a total of 90 persons aged 6 to 17 years (35 boys and 55 girls) who were divided into two groups: the control group (I) included 30 persons of the conventional «clean» territories, and the main group (II) - 60 patients with patho- logy of the digestive organs who were born and live at the RCT. The study program included: the collection of anam- nesis, complaints; clinical and instrumental examinations. The following tests were applied by us: «What things are hidden in the drawings», Toulouse-Pieron, Raven, and Luria testing. For detecting the anxiety level, and the subjec- tive signs of autonomic dysfunctions were used the Spilberg-Hanin self-diagnosis and the Wein questionnaire, respectively., Results: It was shown that in children aged 6-11 years, according to the results of the Toulouse-Pieron test, speed of cognitive information-processing was significantly decreased by 7.17 conventional units, while on the back- ground of the etiopathogenetic treatment of the digestive tract - by 10.24 conventional units relative to the va- lues of the control group. The long-term memory was statistically significantly decreased in the examined children of senior school age (from 12 to 17 years). A significant increase in reactive anxiety and a reverse correlation between the personal anxiety (PA) and speed of cognitive information-processing (r = -0.331) were recorded in patients aged 6-11 years. In older patients, PA was increased.Сonclusions. The obtained results indicate that the state of cognitive functions was characterized by a decrease in speed of cognitive information-processing, long-term memory and a high level of anxiety in children aged from 6 to 17 years residents of RСT with pathology of digestive organs, according to the used testing., (L. M. Lisukha, I. Ye. Kolpakov.)

In this study, we combine heat diffusion equation and modified Hodgkin-Huxley axonal model to investigate how an action potential is generated during infrared neural stimulation. The effects of temporal and spatial distribution of heat induced by infrared pulsed lasers on variation of electrical membrane capacitance are investigated. These variations can lead to depolarize the membrane and generate an action potential. We estimate the threshold values of laser light parameters such as energy density, pulse duration, and repetition rate are needed to trigger an action potential. In order to do it, we present an analytic solution to heat diffusion equation. Then, the analytic results are verified by experimental results. Furthermore, the modified Hodgkin-Huxley axonal model is applied to simulate the generation of action potential during infrared neural stimulation by taking into account the temperature dependence of electrical membrane capacitance. Results show that the threshold temperature increase induced by a train infrared pulse laser can be smaller if repetition rate is higher. These results also indicate that temperature rise time and axon diameter influence on threshold temperature increase. To verify threshold values estimated by the presented method, we use a train infrared pulsed laser (λ = 1450 nm with repetition rate of 3.8 Hz, pulse duration of 18 ms and energy density of 5 J/cm 2 ) to optically pace an adult rat heart, and we are able to successfully pace the rat heart during an open-heart surgery. The presented method can be used to estimate threshold values of laser parameters required for generating an action potential, and it can provide an insight to how the temperature changes lead to neural stimulation during INS.

Photobiomodulation (PBM) is a simple, efficient and cost-effective treatment for both acute and chronic pain. We previously showed that PBM applied to the mouse head inhibited nociception in the foot. Nevertheless, the optimum parameters, location for irradiation, duration of the effect and the mechanisms of action remain unclear. In the present study, the pain threshold in the right hind paw of mice was studied, after PBM (810 nm CW laser, spot size 1 or 6 cm 2 , 1.2-36 J/cm 2 ) applied to various anatomical locations. The pain threshold, measured with von Frey filaments, was increased more than 3-fold by PBM to the lower back (dorsal root ganglion, DRG), as well as to other neural structures along the pathway such as the head, neck and ipsilateral (right) paw. On the other hand, application of PBM to the contralateral (left) paw, abdomen and tail had no effect. The optimal effect occurred 2 to 3 hours post-PBM and disappeared by 24 hours. Seven daily irradiations showed no development of tolerance. Type 1 metabotropic glutamate receptors decreased, and prostatic acid phosphatase and tubulin-positive varicosities were increased as shown by immunofluorescence of DRG samples. These findings elucidate the mechanisms of PBM for pain and provide insights for clinical practice., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-μm-wide beams spaced 100, 200 or 300 μm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96-960 Gy for MRT, and 24-120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver-Barrera staining. The LD 50 and LD 100 when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 μm to 300 μm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

This paper presents an overview of radiobiological dependences governing the occurrence of tissue (organ) reactions that determine the outcomes of chronic exposure to low-LET ionizing radiation (IR) in humans. The mechanisms involved in the development of tissue reactions (TRs) to long-term exposures to IR and radioadaptation are considered. The overview describes the reactions of the haematopoietic, immune, nervous, reproductive and endocrine systems, lungs, skin and crystalline lens to chronic radiation exposure, which are of fundamental importance in view of radiation protection. It is shown that the individual's physiological tissue (organ) reserve, and also that induced by radiation exposure at low-dose rates are of great significance in the context of TR development., (© World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.)

Most results regarding induced current in the human body related to electric field dosimetry have been calculated under uniform field conditions. We have found in previous work that a contact current is a more suitable way to evaluate induced electric fields, even in the case of exposure to non-uniform fields. If the relationship between induced currents and external non-uniform fields can be understood, induced electric fields in nervous system tissues may be able to be estimated from measurements of ambient non-uniform fields. In the present paper, we numerically calculated the induced electric fields and currents in a human model by considering non-uniform fields based on distortion by a cubic conductor under an unperturbed electric field of 1 kV m(-1) at 60 Hz. We investigated the relationship between a non-uniform external electric field with no human present and the induced current through the neck, and the relationship between the current through the neck and the induced electric fields in nervous system tissues such as the brain, heart, and spinal cord. The results showed that the current through the neck can be formulated by means of an external electric field at the central position of the human head, and the distance between the conductor and the human model. As expected, there is a strong correlation between the current through the neck and the induced electric fields in the nervous system tissues. The combination of these relationships indicates that induced electric fields in these tissues can be estimated solely by measurements of the external field at a point and the distance from the conductor.

Ultraviolet (UV) radiation can produce biological damage, leading the cell to apoptosis by the p53 pathway. This study evaluated some molecular markers of the apoptosis pathway induced by UVA, UVB and UVA+ UVB (Solar Simulator, SIM) in environmental doses, during five consecutive days of exposure, in the brain of the crab Ucides cordatus. We evaluated the central nervous system (CNS) by immunoblotting the content of proteins p53, p21, phosphorylated AKT, BDNF, GDNF, activated caspase-3 (C3) and phosphohistone H3 (PH3); and by immunohistochemical tests of the cells labeled for PH3 and C3. After the fifth day of exposure, UVB radiation and SIM increased the protein content of p53, increasing the content of AKT and, somehow, blocking p21, increasing the content of activated caspase-3, which led the cells to apoptosis. The signs of death affected the increase in neurotrophins, such as BDNF and GDNF, stimulating the apoptotic cascade of events. Immunohistochemical assays and immunoblotting showed that apoptosis was present in the brains of all UV groups, while the number of mitotic cells in the same groups decreased. In conclusion, environmental doses of UV can cause apoptosis by increasing p53 and decreasing p21, revealing an UV-damage pathway for U. cordatus., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3⁺CD4(-)CD8⁺ T-cells in the thymus and the proportion of CD3⁺CD4⁺CD8(-) T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation.

Although there is scientific consensus that radiofrequency (RF) exposure at high intensity can cause thermal effects, including well-established adverse health effects, there is still considerable controversy on whether low-intensity RF exposure can cause biological effects, especially adverse health effects. The objective of this paper is to describe several reported "non-thermal" effects that were later shown to be due to a weak thermal effect or an experimental artifact by properly conducted and thorough follow-on scientific research. First, the multiple factors that can cause different RF energy absorption in biological tissues are reviewed and second, several examples of experimental artifacts in published papers are described to demonstrate the importance of paying attention to dosimetry and temperature control. For example, isolated nerve response studies show that when temperature of the RF-exposed tissues is controlled, effects disappeared. During RF exposure, conductive electrodes routinely used in physiological studies have been shown to cause field intensification at the tips or contacts of the electrodes with biological tissue; thus, the RF exposure at the site of measurement could be much higher than the incident field. In some in vitro studies, a lack of temperature uniformity in RF-exposed cell cultures and rate of heating explain changes originally reported to be due to low-level RF exposure. In other studies, detailed dosimetry studies have identified artifacts that explain the reasons why so-called "non-thermal" effects were mistakenly reported. Researchers should look for explanations for their own findings, and not expect others to figure out what was the reason for their observed effects.

Long-term results of randomised trials have confirmed the safety and efficacy of hypofractionated radiotherapy using approximately 2.6 Gy per fraction to lower total doses of 40-42.6 Gy delivered over 3 weeks, for postoperative treatment of early breast cancer. In these trials, hypofractionated radiotherapy was predominantly used for breast only treatment, while there are fewer trials that specifically examined hypofractionated radiotherapy to the breast plus regional nodes. Hypofractionated locoregional radiation is considered a standard of care in the United Kingdom and in some parts of Canada. We aim to review the radiobiology and normal tissue effects of hypofractionated locoregional radiation and to summarize available published clinical experiences using this treatment strategy as adjuvant therapy after breast conserving surgery or mastectomy for women with early breast cancer., (Copyright © 2015. Published by Elsevier SAS.)

Ultraviolet (UV) radiation can produce biological damage, principally oxidative stress, by increasing the production of reactive oxygen species (ROS). This study evaluated biochemical impairments related to the oxidative stress induced by UVA, UVB and UVA+UVB (solar simulator-SIM) in environmental doses, during five consecutive days of exposure, in the brain and eyestalk of the crab Ucides cordatus. We evaluated these regions by sampling on the 1st, 3rd and 5th days of UV exposure for lipid peroxidation (LPO), antioxidant capacity against the peroxyl radical (ACAP), and the activities of catalase (CAT), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Immunohistochemical and immunoblotting assays were performed for anti-activated-caspase 3 in the brains. After the first day of exposure, LPO increased in the eyestalks and brains of the UV-exposed animals; ACAP, and CAT, GPX and GST activities also increased in the brains. On the third day, the LPO values in the eyestalk remained high in the UV-exposed groups, while ACAP decreased in the brain and eyestalk and CAT activity remained high in all irradiated groups in both regions. On the fifth day, LPO decreased in the eyestalk and brain of the UV-exposed groups. These results may have been a consequence of the antioxidant defense system (ADS) activity, since CAT activity was high in both regions, ACAP was high in the eyestalks of the SIM group, and GPX activity remained high in the eyestalks of the UVA and UVB groups. Immunohistochemical assays and immunoblotting showed that there was apoptosis in the brains of the UV-exposed crabs. In conclusion, environmental doses of UV can cause oxidative damage to the CNS cells, including apoptosis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent studies have evaluated the role of direct radiation exposure in neurodegenerative disorders; however, association among indirect effects of radiation and neurodegenerative diseases remains rarely discussed. The objective of this study was to estimate the relative risk of neurodegeneration due to direct and indirect effects of radiation. (60)Co gamma ray was used as source of direct radiation whereas irradiated cell conditioned medium (ICCM) was used to mimic the indirect effect of radiation. To determine the potency of ICCM to inhibit neuronal cells survival colony forming assay was performed. The role of ICCM to induce apoptosis in neuronal SH-SY5Y cells was estimated by TUNEL assay and Annexin V/PI assay. Level of oxidative stress and the concentration of inflammatory cytokines after exposing to direct radiation and ICCM were evaluated by ELISA method. Expression of key apoptotic protein following direct and indirect radiation exposure was investigated by western blot technique. Experimental data manifest that ICCM account loss of cell survival and increase apoptotic induction in neuronal SH-SY5Y cells that was dependent on time and dose. Moreover, ICCM stimulate significant release of inflammatory cytokines i.e., tumor necrosis factor TNF-alpha (P < 0.01), Interleukin-1 (IL-1, P < 0.001), and Interleukin-6 (IL-6, P < 0.001) in neuronal SH-SY5Y cells and elevate the level of oxidative stress (MDA, P < 0.01). Up-regulation of key apoptotic protein expression i.e., Bax, Bid, cytochrome C, caspase-8 and caspase-3 confirms the toxicity of ICCM to neuronal cells. This study provides the evidence that indirect effect of radiation can be as much damaging to neuronal cells as direct radiation exposure can be. Hence, more focused research on estimation risks of indirect effect of radiation to CNS at molecular level may help to reduce the uncertainty about cure and cause of several neurodegenerative disorders.

Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: A compact theory that predicts quantitatively when and where magnetic neurostimulation will occur is needed as a guide to therapy, ideally providing a single equation that defines the target volume of tissue excited by single or dual coils., Methods: A first-principles analysis of magnetic stimulation incorporating a simplified description of electromagnetic fields and a simplified cable theory of the axon yields a mathematical synthesis predicting how to aim., Results: Nerve stimulation produced by a single circular coil having one or more closely packed turns occurs in donut shaped volume of tissue beneath the coil. Axons spanning several millimeters are the sites of magnetic stimulation. The sites of maximal transmembrane depolarization in nerve fibers correspond to points where the axons enter or exit this volume of magnetically induced voltage and current. The axonal membrane at one end is depolarized locally during the rising phase of current in the coil. The axonal membrane at the opposite end is depolarized locally during the falling phase of current in the coil. Penetration depths of several centimeters from the skin surface or approximately one to two coil radii are practical. With two coils placed in a figure-of-eight configuration the separate clockwise and counterclockwise currents generate magnetic fields that add, producing maximal stimulation of a spindle shaped volume, centered at a depth of one-third to one-half coil radius from the body surface., Conclusions: This condensed synthesis of electromagnetic theory and cable theories of axon physiology provides a partial solution to the targeting problem in peripheral and in transcranial magnetic stimulation.

Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy.

Informal surveys at CME meetings have shown that approximately one-third of patients in the United States receive hyperbaric oxygen (HBO2) for delayed radiation injury. More than 600,000 patients receive radiation for malignancy in our country annually, and about one-half will be long-term survivors. Serious radiation complications occur in 5-10% of survivors. A large population of patients is therefore at risk for radiation injury. HBO2 has been applied to treat patients with radiation injury since the mid-1970s. Published results are consistently positive, but the level of evidence for individual publications is usually not high level, consisting mostly of case series and case reports. Only a rare randomized controlled trial has been accomplished. Radiation injury is one of the UHMS "approved" indications, and third-party payors will usually reimburse for this application. This updated review summarizes the publications available reporting results in treating radiation-injured patients. Mechanisms of HBO2 in radiation injury are discussed briefly. Outcome is reported on a mostly anatomic basis though due to the nature of the injury a positive outcome at one anatomic site is supportive of HBO2 at other sites. The potential benefit of prophylactic HBO2 before frank damage is also discussed in high-risk patients. The concerns of HBO2 enhancing growth of or precipitating recurrence of malignancy is discussed and largely refuted.

Purpose of Review: Radiation administered to treat CNS neoplasms or systemic cancers adjacent to the CNS can result in a variety of acute, subacute, and delayed clinical syndromes of the brain and spinal cord. Less commonly, the brachial or lumbosacral plexus or the cranial nerves are damaged by radiation therapy (RT). Cranial blood vessels can also be affected by brain RT, especially when it is administered during childhood and results in delayed vessel structural changes. These disorders are important because their presentation can mimic tumor recurrence. Knowledge of the classic clinical signs, imaging features, and time interval from RT will assist the practitioner in establishing the diagnosis and recommending treatment when appropriate., Recent Findings: The acute and subacute syndromes are temporary. An important subacute syndrome following focal external beam RT in combination with chemotherapy to treat newly diagnosed glioblastoma, termed pseudoprogression, has recently been characterized. In addition, recent clinical experience indicates that the delayed RT-induced CNS syndromes, once considered irreversible, can be treated effectively in some patients., Summary: Recent and ongoing research is lending new insights into the mechanisms of RT-related CNS injury and will hopefully lead to more effective methods for the prevention and treatment of this undesired, but typically unavoidable, complication of RT.

The biological effects of modulated radiofrequency (RF) electromagnetic fields have been a subject of debate since early publications more than 30 years ago, suggesting that relatively weak amplitude-modulated RF electromagnetic fields have specific biological effects different from the well-known thermal effects of RF energy. This discussion has been recently activated by the increasing human exposure to RF fields from wireless communication systems. Modulation is used in all wireless communication systems to enable the signal to carry information. A previous review in 1998 indicated that experimental evidence for modulation-specific effects of RF energy is weak. This article reviews recent studies (published after 1998) on the biological effects of modulated RF fields. The focus is on studies that have compared the effects of modulated and unmodulated (continuous wave) RF fields, or compared the effects of different kinds of modulations; studies that used only one type of signal are not included. While the majority of recent studies have reported no modulation-specific effects, there are a few interesting exceptions indicating that there may be specific effects from amplitude-modulated RF fields on the human central nervous system. These findings warrant follow-up studies., (Copyright © 2011 Wiley-Liss, Inc.)

Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform reirradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models., (Copyright © 2010. Published by Elsevier SAS.)

Contact currents flow from/into a human body when touching an object such as a metal structure with a different electric potential. These currents can stimulate muscle and peripheral nerves. In this context, computational analyses of in situ electric fields caused by the contact current have been performed, while their effectiveness for transient contact currents has not well been investigated. In the present study, using an anatomically based human model, a dispersive finite-difference time-domain model was utilised to computed transient contact current and in situ electric fields from a charged human. Computed in situ electric fields were highly localised in the hand. In order to obtain an insight into the relationship between in situ electric field and electro-stimulation, cell-maximum and 5-mm averaged in situ electric fields were computed and compared with strength-duration curves. The comparison suggests that both measures could be larger than thresholds derived from the strength-duration curves with parameters used in previous studies.

Aim: The aim of this study was to investigate the effects of frequency modulated electromagnetic neural stimulation (FREMS), a recently developed safe and effective treatment of painful diabetic neuropathy, on cutaneous microvascular function., Methods: Thirty-one patients with painful neuropathy were enrolled in a randomised, double-blind, crossover FREMS vs. placebo study; each received two series of 10 treatments of either FREMS or placebo in random sequence within no more than 3 weeks. Patients were studied at baseline, end of FREMS and placebo series, and after 4 months of follow-up. Cutaneous blood flow was measured by laser doppler flowmetry and partial tissue tension of oxygen (TcPO2) and carbonic anhydride (TcPCO2) by oxymetry at the lower extremities in basal resting conditions and as incremental response after thermal stimulation., Results: Crossover analysis showed no consistent differences between FREMS and placebo. After 4-month follow-up, a 52% increase of cutaneous blood flow was observed in resting conditions (P=.0086 vs. baseline), while no differences were observed as incremental flow after warming; compared with baseline, no significant differences were observed for TcPO2 and TcPCO2, both in resting conditions and as incremental response to warm., Conclusion: These results indicate that 10 treatments with FREMS may induce an enhancement of microvascular blood flow measurable at 4 months of follow-up. The findings of this study will need to be confirmed in a larger, adequately powered study (ClinicalTrial.gov Id: NCT00337324).

Purpose: To investigate the effects of static magnetic field (SMF) exposure on the synaptic transmission in a tail-flip circuit of crayfish., Materials and Methods: An O-shaped permanent magnet (35 mT intensity) was placed under the isolated nerve cord of crayfish to provide static magnetic field exposure. Using electrophysiological methods, the excitatory post synaptic potential (EPSP) before and after field exposure in the lateral giant interneuron were measured and compared., Results: The EPSP produced via electrical and chemical synapses in the lateral giant neuron were enhanced after 30 min of SMF exposure (8.08 mT). Perfusion of field-exposed crayfish bath solution or preloading of Ca(2+) chelator and intracellular Ca(2+) release blocker failed to observe the SMF-induced enhancement on EPSP., Conclusions: Exposure of SMF increases the efficacy of synaptic-transmission in crayfish tail-flip escape circuit and this SMF-induced potentiation is a Ca(2+) dependent phenomenon.

Five hundred and thirty-two nanometers laser light evokes neuron-specific electrical responses in identified neurons of Helix ganglia. Such responses are intensity-dependent over the range 25-1500 mW, readily reversible and repeatable. Detailed experiments on the C1 neuron, which is inhibited by 532 nm light, showed that inhibition results from a selective increase in transmembrane Cl(-) ion conductance. Experiments with calcium-sensitive microelectrodes suggest that the response does not result from an increase in [Ca(2+)](i). The change in Cl(-) ion conductance probably occurs in the extensive plasmalemma infoldings of the proximal axon.

In 2002, the Naval Health Research Center Toxicology Detachment began a study to determine the effects of surgically implanted depleted uranium (DU) pellets on adult rat (e.g., P1 generation) health and reproduction. In this report, the effect of implanted DU on adult rat behavior and health is described. Adult Sprague-Dawley (SD) rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm); 20 DU pellets of size 1 x 2 mm approximates to 0.22 kg (0.5 lb) of DU in a 70-kg (154 lb) person. Control animals were implanted with 12 or 20 tantallum (Ta) pellets. The animals were then housed for up to 150 d postimplantation or 20% of an assumed 2-yr life span for rats. The concentration of uranium in urine directly correlated with the number of implanted DU pellets, indicating that DU was migrating into the body from the implanted pellets. Three male and 4 female animals died during the 150-d period of causes apparently not related to DU implantation. Behavioral testing found no definitive evidence of neurobehavioral perturbations associated with DU implantation. Uranium translocated to tissues known to sequester uranium (bone, teeth, and kidneys), but uranium concentrations varied considerably within each dose group and did not follow a dose-response pattern as anticipated. Serum chemistry values were within normal ranges for the SD rat. However, alanine aminotransferase measurements were significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with Ta pellets only. Phosphate measurements were significantly lower for female rats implanted with 20 DU pellets as compared to both sham surgery controls and animals implanted with Ta pellets only. Monocyte ratios were higher in adult rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Mean platelet volume was found to be significantly lower for rats implanted with 20 DU pellets as compared to sham surgery controls but not when compared to animals implanted with 20 Ta pellets. Gross necropsy found no obvious tissue abnormalities in implanted rats, and the weights of major tissues did not differ between Ta- and DU-implanted animals. Histopathologic analysis of major tissues from animals implanted with 0 pellets, 20 Ta pellets, or 20 DU pellets found no differences between treatment groups. The findings of this study indicate that implantation of up to 20 DU pellets in adult rats did not have a significant negative impact on their general health and neurobehavioral capacities when assessed after 150 d of pellet implantation. However, the growing body of data on the potential health effects associated with DU exposure warrants further studies involving higher embedded DU body burdens in conjunction with longer surveillance periods postimplantation.

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats of line Wistar on a background continuous irradiations (dose rate of 2.6 mGy/h within 20 days of pregnancy) eliminated deficiency cognitive functions at posterity. On the basis of the received data it is concluded presence radioembryoprotective actions of melanin in the relation neuro embryotoxic effects of small dozes ionizing radiation. Taking into account small toxicity of melanin, the preparation can be perspective for practical application.

In order to study the function of specific neural circuits, we generated UAS-Channelrhodopsin2 (ChR2) transgenic Drosophila and established a ChR2-based system that enables specific activation of targeted neurons in larval and adult fruit flies with blue light illumination, under the control of a newly designed light source that provides fully programmable stimulation patterns. We showed that stimulating selectively the nociceptor of larvae expressing ChR2 elicited light-induced 'pain' response, confined freely behaving larvae in defined area and directed larva migration along a preset route. In freely behaving adult flies, rapid photoactivation of targeted gustatory sensory neurons, dopaminergic modulatory neurons and motor neurons triggered the proboscis extension response, escaping reflex and changes in the locomotion pattern, respectively, with precise temporal control. This non-invasive method for remote control of animal behaviors also provides a potential tool for conducting 'gain of function' studies toward understanding how animal behaviors are controlled by neural activity.

Prenatal exposure of pregnant dams to oscillating magnetic fields can cause behavioural deficits in their offspring which persist into adulthood. These changes are waveform-specific and may involve nitric oxide. To investigate the interaction between nitric oxide modulation and perinatal magnetic fields, dams were exposed from 2 days before to 14 days after birth to one of six magnetic field conditions (1, 5, 10, 50 or 500 nT or sham) and given either water, 1g/L nitric oxide precursor l-arginine or 0.5 g/L nitric oxide synthase inhibitor n-methylarginine. At weaning (22d), their offspring were placed in the open field for observation. Rats given 50 nT field or 500 nT field+water were hyperactive and showed increased rearing and bodyweight. These strong effects were attenuated or absent in groups given 50 or 500 nT field+n-methylarginine. Groups given sham field+l-arginine were behaviourally similar to animals given 50 or 500 nT field+water. Higher intensity fields showed robust behavioural and physiological effects. In general, these effects were counteracted by co-administration of nitric oxide synthase inhibitor n-methylarginine, which had little effect on its own. Shams given NO precursor l-arginine were highly similar to those given any higher intensity magnetic field. Results support a critical developmental role of NO and the involvement of NO in magnetic field effects.

Background: There is a general concern on the possible hazardous health effects of exposure to radiofrequency electromagnetic radiations (RFR) emitted from mobile phone base station antennas on the human nervous system., Aim: To identify the possible neurobehavioral deficits among inhabitants living nearby mobile phone base stations., Methods: A cross-sectional study was conducted on (85) inhabitants living nearby the first mobile phone station antenna in Menoufiya governorate, Egypt, 37 are living in a building under the station antenna while 48 opposite the station. A control group (80) participants were matched with the exposed for age, sex, occupation and educational level. All participants completed a structured questionnaire containing: personal, educational and medical histories; general and neurological examinations; neurobehavioral test battery (NBTB) [involving tests for visuomotor speed, problem solving, attention and memory]; in addition to Eysenck personality questionnaire (EPQ)., Results: The prevalence of neuropsychiatric complaints as headache (23.5%), memory changes (28.2%), dizziness (18.8%), tremors (9.4%), depressive symptoms (21.7%), and sleep disturbance (23.5%) were significantly higher among exposed inhabitants than controls: (10%), (5%), (5%), (0%), (8.8%) and (10%), respectively (P<0.05). The NBTB indicated that the exposed inhabitants exhibited a significantly lower performance than controls in one of the tests of attention and short-term auditory memory [Paced Auditory Serial Addition Test (PASAT)]. Also, the inhabitants opposite the station exhibited a lower performance in the problem solving test (block design) than those under the station. All inhabitants exhibited a better performance in the two tests of visuomotor speed (Digit symbol and Trailmaking B) and one test of attention (Trailmaking A) than controls. The last available measures of RFR emitted from the first mobile phone base station antennas in Menoufiya governorate were less than the allowable standard level., Conclusions and Recommendations: Inhabitants living nearby mobile phone base stations are at risk for developing neuropsychiatric problems and some changes in the performance of neurobehavioral functions either by facilitation or inhibition. So, revision of standard guidelines for public exposure to RER from mobile phone base station antennas and using of NBTB for regular assessment and early detection of biological effects among inhabitants around the stations are recommended.

The possible risk of electromagnetic radiation (EMR) for nervous system is regularly published from the middle of 20th century. Numbers of neurobiological studies demonstrate that various EMR frequencies induce changes in nervous tissue of experimental animals but the evidence for health effect of EMR to the nervous system remains uncertain. To solve the fundamental questions about possible health hazard of modern technologies, the main producers of EMR, further intensive experimental studies on animals are needed. This review, focused on morphological findings achieved in various experimental animals, demonstrates that blood-brain barrier is the most studied morpho-functional unit of CNS in experiments with EMR. The morphological findings in experimental animals, in many cases controversial, put some evidence on nervous tissue structural damage after the EMR exposure. In spite of numerous literary data a wide range of contemporary neuro-morphological methods waits to be utilized in the EMR experimental paradigm. Using these methods could play an important role in answering the question about possible adverse effects of microwaves on nervous system.

Recent evidence suggests a link between autism and the human mirror neuron system. In this paper, I argue that temporal disruption from the environment may play an important role in the observed mirror neuron dysfunction, leading in turn to the pattern of deficits associated with autism. I suggest that the developing nervous system of an infant may be particularly prone to temporal noise that can interfere with the initial calibration of brain networks such as the mirror neuron system. The most likely source of temporal noise in the environment is artificially generated electromagnetic radiation. To date, there has been little evidence that electromagnetic radiation poses a direct biological hazard. It is clear, however, that time-varying electromagnetic waves have the potential to temporally modulate the nervous system, particularly when populations of neurons are required to act together. This modulation may be completely harmless for the fully developed nervous system of an adult. For an infant, this same temporal disruption might act to severely delay or disrupt vital calibration processes.

Neurotoxicity from radiation can range widely and produce effects that may include (1) small absolute increases in cancer risks, (2) subtle effects on higher level functioning in some individuals, (3) severe cognitive impairment in some individuals, (4) severe focal injury tat may include necrosis or irreversible loss of function, and (5) overwhelming and rapidly fatal diffuse injury associated with high-dose, whole-body exposures. An understanding of the implications of nervous system exposure to radiation can guide efforts in radiation protection and aid in the optimization of the medical uses of radiation.

After more than two decades of intensive research, the physiological mechanisms of animal magnetoreception remain enigmatic. The primary magnetoreceptors are still unknown and our knowledge of the neural substrate subserving magnetic orientation is meagre. Here we argue that this dismal outcome can be largely attributed to the fact that the potential of recently available neurobiological techniques has not been utilized, review some of these techniques and propose a step by step scenario for future research, concentrating on the heuristic potential of instrumentalizing inducible transcription factors (ITFs) such as Jun, Fos, Fos-related antigens and Krox. ITFs can be used as markers of neuronal activation in experiments on freely moving animals performing magnetically based orientation tasks, in experiments on anaesthetised or restrained animals stimulated magnetically, and in experiments employing treatments that specifically disrupt magnetoreception. Therefore they can serve as tools for identifying neurons involved in the detection and processing of magnetic information. When used in combination with other neurobiological tools, ITFs can also be useful for a more comprehensive description of the involved neural networks, for the identification of magnetoreceptors and, in the case of the photoreceptor-based mechanism, also for studying the involvement of specific light-sensitive molecules in the primary transduction process of magnetoreception. Limitations and pitfalls of the proposed approach are also discussed.

The technology used for magnetic resonance (MR) procedures has evolved continuously during the past 20 years, yielding MR systems with stronger static magnetic fields, faster and stronger gradient magnetic fields, and more powerful radiofrequency transmission coils. Most reported cases of MR-related injuries and the few fatalities that have occurred have apparently been the result of failure to follow safety guidelines or of use of inappropriate or outdated information related to the safety aspects of biomedical implants and devices. To prevent accidents in the MR environment, therefore, it is necessary to revise information on biologic effects and safety according to changes that have occurred in MR technology and with regard to current guidelines for biomedical implants and devices. This review provides an overview of and update on MR biologic effects, discusses new or controversial MR safety topics and issues, presents evidence-based guidelines to ensure safety for patients and staff, and describes safety information for various implants and devices that have recently undergone evaluation., (Copyright RSNA, 2004)

Health effects of radiofrequency radiations (RFR) including mobile phone technology and the adequacy of their safety standards remain uncertain. Case reports of peripheral neurological effects of RFR describe mainly disturbances of noxious sensation (dysaesthesia). Cases associated with other RFR sources as well as mobile phone technology are examined seeking insights into neurophysiological mechanisms and safety levels. Cases have arisen after exposure to much of the frequency range (low MHz to GHz). In some instances symptoms are transitory, but may be lasting in others. After very high intensity exposures nerves may be grossly injured. However, after lower intensity exposures which may result in dysaesthesia, ordinary nerve conduction studies demonstrate no abnormality although current perception threshold studies may. Only a small proportion of similarly exposed persons develop symptoms. The role of modulations (e.g. pulses) needs clarification. Some of these observations are not consistent with the prevailing hypothesis that all health effects of RFR arise from thermal mechanisms. It is concluded that RFR from mobile phones can cause peripheral neurophysiological changes in some persons. The effects occur at exposure levels below the present safety levels for RFR. Possible non-thermal mechanisms are discussed and may point to future directions of research.

Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues.

Studies have evaluated the electroencephalography (EEG) of humans and laboratory animals during and after Radiofrequency (RF) exposures. Effects of RF exposure on the blood-brain barrier (BBB) have been generally accepted for exposures that are thermalizing. Low level exposures that report alterations of the BBB remain controversial. Exposure to high levels of RF energy can damage the structure and function of the nervous system. Much research has focused on the neurochemistry of the brain and the reported effects of RF exposure. Research with isolated brain tissue has provided new results that do not seem to rely on thermal mechanisms. Studies of individuals who are reported to be sensitive to electric and magnetic fields are discussed. In this review of the literature, it is difficult to draw conclusions concerning hazards to human health. The many exposure parameters such as frequency, orientation, modulation, power density, and duration of exposure make direct comparison of many experiments difficult. At high exposure power densities, thermal effects are prevalent and can lead to adverse consequences. At lower levels of exposure biological effects may still occur but thermal mechanisms are not ruled out. It is concluded that the diverse methods and experimental designs as well as lack of replication of many seemingly important studies prevents formation of definite conclusions concerning hazardous nervous system health effects from RF exposure. The only firm conclusion that may be drawn is the potential for hazardous thermal consequences of high power RF exposure., (Published 2003 Wiley-Liss, Inc.)