Biological Effects of Ionizing RadiationBiological Effects of Ionizing RadiationDeterministic effectsDeterministic effects

Neurovascular systemNeurovascular systemLectureLecture

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

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IntroductionIntroduction

Damage of neurovascular system by Damage of neurovascular system by ionizing radiation – one of the typical ionizing radiation – one of the typical consequence of whole body exposureconsequence of whole body exposure

Development of damage had different Development of damage had different stages and symptomsstages and symptoms

Symptoms of neurovascular damage Symptoms of neurovascular damage should be taken into account in diagnosis should be taken into account in diagnosis and treatmentand treatment

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ContentContent

RRadiosensitivity of central nervous cellsadiosensitivity of central nervous cells Early effects of ionizing radiation on Early effects of ionizing radiation on

CNSCNS Late and chronic effects of ionizing Late and chronic effects of ionizing

radiation on CNSradiation on CNS Symptoms of CNS damageSymptoms of CNS damage

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OverviewOverview Central Nervous System (CNS): Central Nervous System (CNS):

radioresistant or radiosensitive?radioresistant or radiosensitive? Symptoms of all phases of acute radiation Symptoms of all phases of acute radiation

illness are connected with involvement of illness are connected with involvement of CNS:CNS: Emesis,Emesis, Nausea,Nausea, Anorexia,Anorexia, Fatigue, Fatigue, Weakness, and Weakness, and Disorientation Disorientation

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Radiosensitive of central nervous Radiosensitive of central nervous cellscells

Effects on neuronsEffects on neurons Effects on glial cellsEffects on glial cells Effects on white and grey matterEffects on white and grey matter

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Effects on neuronsEffects on neurons

Different radiation response of the Different radiation response of the various parts of neuron:various parts of neuron: PerycarionPerycarion DendritesDendrites AxonAxon SynapsesSynapses

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Different radiation response of the Different radiation response of the various parts of neuronvarious parts of neuron

PerycarionPerycarion Cells with small perycarions are more Cells with small perycarions are more

radioresistant because of a better repair radioresistant because of a better repair capacitycapacity

DendritesDendrites Are very resistantAre very resistant

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Different radiation response of the Different radiation response of the various parts of neuronvarious parts of neuron

AxonAxon Are highly resistantAre highly resistant

SynapsesSynapses Different temporary changes in membrane Different temporary changes in membrane

permeability are happening after exposure:permeability are happening after exposure: membrane permeability for potassium and sodium, liberation of pharmacologically active substances

like serotonine and acetylcholine, and interaction between lipoproteins and free radicals

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Effects on glial cellsEffects on glial cells

Radiation response of the various Radiation response of the various glial cells:glial cells: AstrocytesAstrocytes OligodendrocytesOligodendrocytes Microglial cellsMicroglial cells Schwann cellsSchwann cells

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Effects on white and grey matterEffects on white and grey matter

White matter is more sensitive to White matter is more sensitive to ionizing radiation than grey matterionizing radiation than grey matter

Consequences:Consequences: Vascular damageVascular damage Radiation necrosis of the white matter Radiation necrosis of the white matter

because of because of demyelination, which is due demyelination, which is due to the damage of oligodendrocytesto the damage of oligodendrocytes

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Early effects of ionizing radiation Early effects of ionizing radiation on CNSon CNS

Pathophysiological alterationsPathophysiological alterations Vascular system alterationVascular system alteration Biochemical alterationsBiochemical alterations

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Pathophysiological alterationsPathophysiological alterations

The symptoms which are the reflection of The symptoms which are the reflection of pathophysiological alteration:pathophysiological alteration: VomitingVomiting Change in behaviorChange in behavior Electrophysiological modifications Electrophysiological modifications

The symptoms are:The symptoms are: Dose related, and Dose related, and Likely caused by cerebral oedema and Likely caused by cerebral oedema and

increased intracranial pressureincreased intracranial pressure

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Early symptoms of CNS damageEarly symptoms of CNS damage

VomitingVomiting Stages of vomiting:Stages of vomiting:

NauseaNausea RetchingRetching Emesis Emesis

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Early symptoms of CNS damageEarly symptoms of CNS damage

Behavioral changesBehavioral changes Deficits of memory and attention:Deficits of memory and attention:

are proved by diminished performance on are proved by diminished performance on neuropsychological tests involving: neuropsychological tests involving: information processing speed, recent memory and learning performance, sustained vigilance, attention and concentration, problem solving capacity, and executive functions

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Early symptoms of CNS damageEarly symptoms of CNS damage

Electrophysiological modificationsElectrophysiological modifications morphological changes in the brain morphological changes in the brain

occur with doses of several ten of Gy, occur with doses of several ten of Gy, after a latent period of several months after a latent period of several months or yearsor years

the threshold for histological CNS the threshold for histological CNS damage was estimated to be 30-40 Gy if damage was estimated to be 30-40 Gy if the radiation is given in fractionsthe radiation is given in fractions

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Vascular system alterationVascular system alteration DDamage to fine vasculatureamage to fine vasculature Impairment of the capillaries circulationImpairment of the capillaries circulation Increased capillary permeabilityIncreased capillary permeability Plasmatic transudationPlasmatic transudation Pericapillary and interstitial oedema and acute Pericapillary and interstitial oedema and acute

inflammationinflammation Oedematous loosening and hypertrophy of Oedematous loosening and hypertrophy of

perivascular astrocytes and nervous tissue, with perivascular astrocytes and nervous tissue, with damage to the blood-brain barrierdamage to the blood-brain barrier

Some rupture of the capillary walls with petechial Some rupture of the capillary walls with petechial haemorrhageshaemorrhages

Vasculitis with spotty endothelial damageVasculitis with spotty endothelial damage Meningitis and choroid plexitisMeningitis and choroid plexitis

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Blood vessels and blood-brain Blood vessels and blood-brain barrierbarrier

Radiation damage to the blood Radiation damage to the blood vessels:vessels: HaemorrhageHaemorrhage Capillary endothelial vacuolizationCapillary endothelial vacuolization VasculitisVasculitis Capillary permeabilityCapillary permeability

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Biochemical alterationsBiochemical alterations

Could be explained by the Could be explained by the involvement of:involvement of: NeurotransmittersNeurotransmitters CytokinesCytokines

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Late and chronic effects of Late and chronic effects of ionizing radiation on CNSionizing radiation on CNS

Changes in behaviorChanges in behavior Electrophysiological modificationsElectrophysiological modifications Histological changesHistological changes

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Changes in behaviorChanges in behavior

Were studied among clean-up Were studied among clean-up workers of the Chernobyl accidentworkers of the Chernobyl accident

Observations:Observations: neurocircular dystonia neurocircular dystonia diencephal crisisdiencephal crisis presence of different polyneuropathic presence of different polyneuropathic

manifestations manifestations

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Electrophysiological modificationsElectrophysiological modifications

Were studied among clean-up workers of Were studied among clean-up workers of the Chernobyl accident the Chernobyl accident using using neuropsychological and neuropsychological and electrophysiological approaches electrophysiological approaches

Observations:Observations: disturbances of hemispheric interactiondisturbances of hemispheric interaction signs of the left-hemispheric dysfunction signs of the left-hemispheric dysfunction

depend on the brainstem damage while the depend on the brainstem damage while the right-hemispheric dysfunctions are explained right-hemispheric dysfunctions are explained by the diencephalic damageby the diencephalic damage

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Histological changesHistological changes 1-st year following the exposure:1-st year following the exposure:

selective coagulation necrosis in the white selective coagulation necrosis in the white mattermatter

After the 1-st year:After the 1-st year: minute focal areas of necrosis in the white minute focal areas of necrosis in the white

mattermatter vascular degeneration, marked by vascular degeneration, marked by

telangiectasia, hyaline, capillary proliferation, telangiectasia, hyaline, capillary proliferation, wall thickening, perivascular oedema, wall thickening, perivascular oedema, thrombosis, and petichial haemorrhagethrombosis, and petichial haemorrhage

a generalized and progressive atrophy of the a generalized and progressive atrophy of the nervous tissuenervous tissue

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SummarySummary

This lecture presented materials about This lecture presented materials about radiation injury of neurovascular systemradiation injury of neurovascular system

The following topics were covered in The following topics were covered in the lecture: the lecture: radiosensitivity of central radiosensitivity of central nervous cells, early and late effects of nervous cells, early and late effects of ionizing radiation on CNS, symptoms of ionizing radiation on CNS, symptoms of CNS damageCNS damage

Comments are welcomedComments are welcomed

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Where to Get More InformationWhere to Get More Information CChiang CS, Hong JH, Stalder A, Sun JR, Withers HR, hiang CS, Hong JH, Stalder A, Sun JR, Withers HR,

McBride WH. Delayed molecular responses to brain McBride WH. Delayed molecular responses to brain irradiation. Int. J. Radiat. Biol. 1997; 72: 45-53.irradiation. Int. J. Radiat. Biol. 1997; 72: 45-53.

Egana E. Some effects of ionizing radiations on the Egana E. Some effects of ionizing radiations on the metabolism of the central nervous system. Int. metabolism of the central nervous system. Int. J.Neurol. 1962; 3: 631-47.J.Neurol. 1962; 3: 631-47.

Zeman W, Samorajski T. Effects of irradiation on the Zeman W, Samorajski T. Effects of irradiation on the nervous system. Pathology of irradiation. Berdjis nervous system. Pathology of irradiation. Berdjis CC Ed. Williams & Wilkin, Baltimore 1971; 277.CC Ed. Williams & Wilkin, Baltimore 1971; 277.

Zhavoronkova LA et al. Electroencephalographic Zhavoronkova LA et al. Electroencephalographic correlates of neurological disturbances at remote correlates of neurological disturbances at remote periods of the effect of ionizing radiation (sequelae periods of the effect of ionizing radiation (sequelae of the Chernobyl NPP accident). Neurosci. Behav. of the Chernobyl NPP accident). Neurosci. Behav. Physiol. 1995, 25; 2: 142-9.Physiol. 1995, 25; 2: 142-9.