1. Biological Effects of Ionizing Radiation Deterministic effects Neurovascular system Lecture IAEA Post Graduate Educational Course Radiation Protection and Safe Use of Radiation Sources IAEA Post Graduate Educational Course in Radiation Protection and Safety of Radiation Sources

2. Add module code number and lesson title2 Introduction l Damage of neurovascular system by ionizing radiation – one of the typical consequence of whole body exposure l Development of damage had different stages and symptoms l Symptoms of neurovascular damage should be taken into account in diagnosis and treatment

3. Add module code number and lesson title3 Content l R adiosensitivity of central nervous cells l Early effects of ionizing radiation on CNS l Late and chronic effects of ionizing radiation on CNS l Symptoms of CNS damage

4. Add module code number and lesson title4 Overview l Central Nervous System (CNS): radioresistant or radiosensitive? l Symptoms of all phases of acute radiation illness are connected with involvement of CNS: n Emesis, n Nausea, n Anorexia, n Fatigue, n Weakness, and n Disorientation

5. Add module code number and lesson title5 Radiosensitive of central nervous cells l Effects on neurons l Effects on glial cells l Effects on white and grey matter

6. Add module code number and lesson title6 Effects on neurons l Different radiation response of the various parts of neuron: n Perycarion n Dendrites n Axon n Synapses

7. Add module code number and lesson title7 Different radiation response of the various parts of neuron l Perycarion n Cells with small perycarions are more radioresistant because of a better repair capacity l Dendrites n Are very resistant

8. Add module code number and lesson title8 Different radiation response of the various parts of neuron l Axon n Are highly resistant l Synapses n Different temporary changes in membrane permeability are happening after exposure: s membrane permeability for potassium and sodium, s liberation of pharmacologically active substances like serotonine and acetylcholine, and s interaction between lipoproteins and free radicals

9. Add module code number and lesson title9 Effects on glial cells l Radiation response of the various glial cells: n Astrocytes n Oligodendrocytes n Microglial cells n Schwann cells

10. Add module code number and lesson title10 Effects on white and grey matter l White matter is more sensitive to ionizing radiation than grey matter l Consequences: n Vascular damage n Radiation necrosis of the white matter because of demyelination, which is due to the damage of oligodendrocytes

11. Add module code number and lesson title11 Early effects of ionizing radiation on CNS l Pathophysiological alterations l Vascular system alteration l Biochemical alterations

12. Add module code number and lesson title12 Pathophysiological alterations l The symptoms which are the reflection of pathophysiological alteration: n Vomiting n Change in behavior n Electrophysiological modifications l The symptoms are: n Dose related, and n Likely caused by cerebral oedema and increased intracranial pressure

13. Add module code number and lesson title13 Early symptoms of CNS damage l Vomiting l Stages of vomiting: n Nausea n Retching n Emesis

14. Add module code number and lesson title14 Early symptoms of CNS damage l Behavioral changes l Deficits of memory and attention: n are proved by diminished performance on neuropsychological tests involving: s information processing speed, s recent memory and learning performance, s sustained vigilance, s attention and concentration, s problem solving capacity, and sexecutive functions

15. Add module code number and lesson title15 Early symptoms of CNS damage l Electrophysiological modifications n morphological changes in the brain occur with doses of several ten of Gy, after a latent period of several months or years n the threshold for histological CNS damage was estimated to be 30-40 Gy if the radiation is given in fractions

16. Add module code number and lesson title16 Vascular system alteration l Damage to fine vasculature l Impairment of the capillaries circulation l Increased capillary permeability l Plasmatic transudation l Pericapillary and interstitial oedema and acute inflammation l Oedematous loosening and hypertrophy of perivascular astrocytes and nervous tissue, with damage to the blood-brain barrier l Some rupture of the capillary walls with petechial haemorrhages l Vasculitis with spotty endothelial damage l Meningitis and choroid plexitis

17. Add module code number and lesson title17 Blood vessels and blood-brain barrier l Radiation damage to the blood vessels: n Haemorrhage n Capillary endothelial vacuolization n Vasculitis n Capillary permeability

18. Add module code number and lesson title18 Biochemical alterations l Could be explained by the involvement of: n Neurotransmitters n Cytokines

19. Add module code number and lesson title19 Late and chronic effects of ionizing radiation on CNS l Changes in behavior l Electrophysiological modifications l Histological changes

20. Add module code number and lesson title20 Changes in behavior l Were studied among clean-up workers of the Chernobyl accident l Observations: n neurocircular dystonia n diencephal crisis n presence of different polyneuropathic manifestations

21. Add module code number and lesson title21 Electrophysiological modifications l Were studied among clean-up workers of the Chernobyl accident using neuropsychological and electrophysiological approaches l Observations: n disturbances of hemispheric interaction n signs of the left-hemispheric dysfunction depend on the brainstem damage while the right-hemispheric dysfunctions are explained by the diencephalic damage

22. Add module code number and lesson title22 Histological changes l 1-st year following the exposure: n selective coagulation necrosis in the white matter l After the 1-st year: n minute focal areas of necrosis in the white matter n vascular degeneration, marked by telangiectasia, hyaline, capillary proliferation, wall thickening, perivascular oedema, thrombosis, and petichial haemorrhage n a generalized and progressive atrophy of the nervous tissue

23. Add module code number and lesson title23 Summary l This lecture presented materials about radiation injury of neurovascular system l The following topics were covered in the lecture: radiosensitivity of central nervous cells, early and late effects of ionizing radiation on CNS, symptoms of CNS damage l Comments are welcomed

24. Add module code number and lesson title24 Where to Get More Information l Chiang CS, Hong JH, Stalder A, Sun JR, Withers HR, McBride WH. Delayed molecular responses to brain irradiation. Int. J. Radiat. Biol. 1997; 72: 45-53. l Egana E. Some effects of ionizing radiations on the metabolism of the central nervous system. Int. J.Neurol. 1962; 3: 631-47. l Zeman W, Samorajski T. Effects of irradiation on the nervous system. Pathology of irradiation. Berdjis CC Ed. Williams & Wilkin, Baltimore 1971; 277. l Zhavoronkova LA et al. Electroencephalographic correlates of neurological disturbances at remote periods of the effect of ionizing radiation (sequelae of the Chernobyl NPP accident). Neurosci. Behav. Physiol. 1995, 25; 2: 142-9.