Threshold for radiation-related severe mental retardation in prenatally exposed A-bomb survivors: a re-analysis

Author: Otake M., Schull W.J., Lee S.

Reference: Int. J. Radiat. Biol. — 1996. — Vol.70, № 6. — P. 755–763.

Keywords: 8th-25th week after ovulation, mental effects

Abstract: Significant effects on the developing human brain of exposure to ionizing radiation are seen among individuals exposed in the 8th-25th week after ovulation. These effects, particularly in the highly vulnerable period of 8-15 weeks after ovulation, manifest themselves most dramatically as an increased frequency of severe mental retardation. However, the distribution of cases of severe mental retardation suggests a threshold in the low-dose region. The 95% lower bound of the threshold in those survivors exposed 8-15 weeks after ovulation was zero for the individual data based on the simple linear model, and 0.15 Gy based on the exponential linear model used in our previous report (1987), but the 95% lower bound of the threshold based on all of the data including 21 additional cases with known doses appears to be 0.05 Gy using the maximum likelihood estimates derived from an exponential-linear model. The latter model was selected because it provides the best fit from the standpoint of the stableness and reasonableness of the estimates among the five models applied to the data. When two probably non-radiation-related cases of Down’s syndrome are excluded from the 19 mentally retarded cases exposed 8-15 weeks post ovulation, the 95% lower bound of the threshold is in the range of 0.15-0.25 Gy based on the exponential-linear model used in 1987, but is in the range of 0.06-0.31 Gy when the more reasonable and better model applied here is used. For exposure in the 16-25-week period based on the same model, the 95% lower bound of the threshold changed from 0.25 to 0.28 Gy, both with and without inclusion of the two probable non-radiation-related mentally retarded cases; one of these cases was probably familial in origin since there was a retarded sibling, and the other due to infection, since the individual had Japanese B encephalitis at age 4 years.

URL: http://www.ncbi.nlm.nih.gov/pubmed/8980673

Neuron loss during early adulthood following prenatal low-dose X-irradiation in the mouse brain

Author: H. Korr, H. Thorsten Rohde, J. Benders et al.

Reference: Int. J. Radiat. Biol. — 2001. — Vol. 77, № 5. — P. 567–580.

Keywords: prenatal low-dose X-irradiation, hippocampal pyramidal cells

Abstract: PURPOSE: Apart from subsequent cell death, little is known about long-term effects of a prenatal low-dose X-irradiation (PLDI) on nuclear (n) and mitochondrial (mt) DNA, and whether these effects are connected with reduced neuron numbers in the adult brain.

MATERIALS AND METHODS: Pregnant mice were X-irradiated with 0, 10 or 50cGy at day 13 (E13) of pregnancy. One day after (E14), or postnatally at day 25 (P25) or P180, the brains of the offspring were analysed concerning the extent of nDNA repair, mt biogenesis, and the relative content of nDNA single strand breaks (SSB). Stereology was applied for evaluating neuronal loss.

RESULTS: One day after irradiation no unrepaired SSB were detected. Significant results were mainly obtained for hippocampal pyramidal cells at P180, particularly cell loss following 50 cGy PLDI, increased SSB content and mt biogenesis (0 vs. 10cGy) but decreased mt biogenesis for 10 vs. 50 cGy.

CONCLUSIONS: A hypothesis closely related to that regarding molecular events during aging is presented for explaining this second wave of cell death in adult mice following PLDI as a result of accumulated mtDNA damage caused by PLDI. A possible relation to the neurodegenerative hypothesis of schizophrenia is discussed.

URL: http://www.ncbi.nlm.nih.gov/pubmed/11382335

Neuro-inflammatory response in rats chronically exposed to (137)Cesium

Author: P. Lestaevel, L. Grandcolas, F. Paquet et al.

Reference: Neurotoxicology. ― 2008. ― Vol. 29, № 2. ― P. 343–348.

Keywords: CNS, Cs137, inflammatory cytokine genes, electrophysiological alterations

Abstract: After the Chernobyl nuclear accident, behavioural disorders and central nervous system diseases were frequently observed in populations living in the areas contaminated by (137)Cs. Until now, these neurological disturbances were not elucidated, but the presence of a neuro-inflammatory response could be one explanation. Rats were exposed for 3 months to drinking water contaminated with (137)Cs at a dose of 400Bqkg(-1), which is similar to that ingested by the population living in contaminated areas in the former USSR countries. Pro-inflammatory and anti-inflammatory cytokine genes were assessed by real-time PCR in the frontal cortex and the hippocampus. At this level of exposure, gene expression of TNF-alpha and IL-6 increased in the hippocampus and gene expression of IL-10 increased in the frontal cortex. Concentration of TNF-alpha, measured by ELISA assays, was also increased in the hippocampus. The central NO-ergic pathway was also studied: iNOS gene expression and cNOS activity were significantly increased in the hippocampus. In conclusion, this study showed for the first time that sub-chronic exposure with post-accidental doses of (137)Cs leads to molecular modifications of pro- and anti-inflammatory cytokines and NO-ergic pathway in the brain. This neuro-inflammatory response could contribute to the electrophysiological and biochemical alterations observed after chronic exposure to (137)Cs.

URL: http://www.ncbi.nlm.nih.gov/pubmed/18295892

Neuroimmune and gene expression changes in chronic fatigue syndrome after the low-dose radiation exposure

Author: D. Bazyka, K. Loganovsky, I. Ilyenko et al.

Reference: 8^th International LOWRAD Conference «The Effects of Low Doses and Very Low Doses of Ionizing Radiation on Human Health and Biotopes», 28–30 September 2009, Rio de Janeiro, Brazil. — P. 117.

Radiation injury and neurogenesis

Author: Monje M.L. Palmer T.

Reference : Curr. Opin. Neurol. ― 2003. ― Vol. 16, № 2. ― P. 129–134.

Keywords: vasculopathy, CNS, hippocampal formation, cranium

Abstract: PURPOSE OF REVIEW: For many cancers, survival depends on aggressive combined therapies, but treatment comes at a price. Children and adults who receive radiotherapy involving the brain frequently experience a progressive cognitive decline. The overt pathologies of radiation injury such as white matter necrosis or vasculopathy are the obvious “smoking guns” of dysfunction. However, many patients exhibit severe learning and memory deficits with no overt pathologic changes. This is especially true when the radiation field involves the temporal lobes. The cause of this debilitating dysfunction is currently unknown and untreatable.

RECENT FINDINGS: Within the temporal lobe, the hippocampal formation plays a central role in short-term learning and memory–the functions most notably affected by radiation. Recent work has also shown that hippocampus-dependent learning and memory are strongly influenced by the activity of neural stem cells and their proliferative progeny. The hippocampal granule cell layer undergoes continuous renewal and restructuring by the addition of new neurons. Radiation at much lower doses than that needed to injure the more resistant post-mitotic neurons and glia of the brain has been found to affect these highly proliferative progenitors severely. The stem/progenitor cell is so sensitive to radiation that a single low dose to the cranium of a mature rat is sufficient to ablate hippocampal neurogenesis.

SUMMARY: Progressive learning and memory deficits following irradiation may be caused by the accumulating hippocampal dysfunction that results from a long-term absence of normal stem/progenitor activity. Here, the authors describe the nature of this stem cell dysfunction and contemplate how restoration of stem/progenitor cell activity might be approached in experimental models and, eventually, the clinic.

URL: http://www.ncbi.nlm.nih.gov/pubmed/12644738

Lymphocyte apoptosis control and neurodegeneration at the late period after the acute radiation syndrome

Author: D. Bazyka, I. Ilyenko, K. Loganovsky et al.

Reference: Abstracts of 17^th ECDO Euroconference on apoptosis «Destruction, degradation and death cell death control in cancer and neurodegeneration», September 23–26, 2009, Institut Pasteur, Paris, France. — P. 63.

Long-lasting cerebral functional changes following moderate dose X-radiation treatment to the scalp in childhood: an electroencephalographic power spectral study

Author: I. Yaar, E. Ron, B. Modan et al.

Reference: J. Neurol. Neurosurg. Psychiatry. — 1982. — Vol. 45, № 2. — P. 166–169.

Keywords: EEG, visual analyses, tinea capitis treatment

Abstract: EEG tracings were compared in 44 young adults who received scalp x-radiation treatment for tinea capitis during childhood and 59 non-irradiated control subjects. The irradiated subjects were exposed, over 20 years previously, to a mean dose of 130 rads to the brain. Visual analysis of the EEG revealed an insignificant excess of abnormalities among the irradiated subjects compared to the controls. Power spectral density function analysis showed increased power values among the irradiated subjects, particularly in the beta wave frequencies. This finding provides further evidence for suspecting that x-irradiation during brain maturation may cause long-lasting damage to the brain tissue. (full text in English available on web)

URL: http://jnnp.bmj.com/content/45/2/166.long

Cerebral basis of posttraumatic stress disorder following the Chernobyl disaster.

Author: Loganovsky KN, Zdanevich NA.

Reference: CNS Spectr. 2013, 18 (2): 95–102.

Keywords: PTSD, cerebrovascular pathology, hippocampus, depression

Abstract: BACKGROUND: Whether posttraumatic stress disorder (PTSD) following radiation emergency has psychopathological, neurocognitive, and neurophysiological peculiarities is at issue.

OBJECTIVE: The goal was to explore the features and cerebral basis of “radiation” PTSD in the survivors of the Chernobyl accident. Subjects and Methods The cross-sectional study included 241 people, 219 of whom have been diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria, among them 115 clean-up workers of the Chernobyl accident (34 with acute radiation sickness), 76 evacuees from the Chernobyl exclusion zone, 28 veterans of the war in Afghanistan, and 22 healthy unexposed individuals. Psychometric examinations, neurocognitive assessments, computerized electroencephalography, and cerebral vascular Doppler were used.

RESULTS: “Radiation” PTSD includes “flashforward” phenomena and anticipating stress (projection of fear and danger to the future); somatoform disorders (depression, trait and state anxiety); and neurocognitive deficit (impaired memory and attention, auditory-verbal memory and learning, proactive and retroactive interference, cerebellar and stem symptoms, intellectual changes). The intima-media component, thickness of common carotid arteries, and common and left internal carotid arteries stenosis rates are increased in the liquidators. Changes of bioelectrical brain activity as a decrease of beta- and theta-power, together with an increase of alpha-power, were found in the Chernobyl accident survivors with PTSD.

CONCLUSIONS: PTSD following radiation emergency is characterized by comorbidity of psychopathology, neurocognitive deficit, and cerebrovascular pathology with increased risk of cerebral atherosclerosis and stroke. The cerebral basis of this PTSD is proposed to be an abnormal communication between the pyramidal cells of the neocortex and the hippocampus, and deep brain structures. It is recommended that a system of emergency and long-term psychological and psychiatric care be organized for the survivors in Fukushima Daichi, Japan.

URL: http://www.ncbi.nlm.nih.gov/pubmed/23445934

Intelligence deterioration following acute radiation sickness.

Author: Loganovsky K.N., Zdorenko L.L.

Reference: Clinical Neuropsychiatry. — 2012. — Vol. 9, № 5. — P. 187-194

Keywords: IQ, cognitive impairment, ARS

Abstract: Full text in English available on web.

URL: http://www.clinicalneuropsychiatry.org/pdf/Loganovsky_sito.pdf

Loganovsky K.N., Yuryev K.L. EEG patterns in persons exposed to ionizing radiation as a result of the Chernobyl accident. Part 2: quantitative EEG analysis in patients who had acute radiation sickness

Author: Loganovsky K.N., Yuryev K.L.

Reference: J. Neuropsychiatry Clin. Neurosci. — 2004. — Vol. 16, № 1. — P. 70–82.

Keywords: qEEG, neurophysiological markers, left fronto-temporal dominant frequency reduction

Abstract: Cross-sectional quantitative electroencephalogram (qEEG) study (1996—2001) among Chernobyl accident survivors, who had confirmed acute radiation sickness and were irradiated in dose of 1—5 Gy, revealed the neurophysiological markers of ionizing radiation. Neuropsychological markers were: left fronto-temporal dominant frequency reduction; absolute δ-power lateralization to the left (dominant) hemisphere; relative δ-power increase in the fronto-temporal areas; absolute θ-power decrease in the left temporal region; absolute and relative α-power diffusive decrease, which may reflect cortico-limbic dysfunction lateralized to the left, dominant hemisphere, with the fronto-temporal cortical and hippocampal damage. Quantitative electroencephalogram proposed for differentiation of radiation and nonradiation brain damages and as a new biological dosymetry method. High radiosensitivity of the brain, neocortex, and dominant hemisphere higher radiosensitivity are discussed.

URL: http://neuro.psychiatryonline.org/article.aspx?articleID=101854