CSIRO - June 1994
BIOLOGICAL EFFECTS AND SAFETY OF EMR
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8.0 EFFECTS OF EMR ON CENTRAL NERVOUS SYSTEM
SUMMARY
From studies on human perception it is accepted that very low levels of microwave exposure elicit a response, known as microwave hearing, that is thought to be due to a thermoelastic change producing a pressure wave in the brain and auditory sensory apparatus. It would not be too surprising to find associated transitory changes in the electrocortical activity, although the results in humans and animals are equivocal probably due to artefacts in experimental technique. There have been contradictory reports (by the same group of researchers) on the effect of microwave radiation on the permeability of the blood-brain barrier, making sensible interpretation rather difficult.
Changes in animal behaviour induced by high exposures (SAR > 4 W/kg) create a significant increase in body temperature and would, therefore, invoke a response in the hypothalamus and adrenal corticosteroids. Other sensitive endocrine organs such as the pituitary and pineal glands would also respond to such a gross physical insult.
Of more interest from a human health perspective are the reports of impaired learning and memory function in rats following a exposure to relatively low level SAR 0.6 W/kg. The effect has been shown to be due to microwave-induced activation of brain opiod activity. Such subtle neurophysiological responses are of particular interest. Alterations in DNA arrangement have also been detected by sensitive electrophoretic tests, following exposure to similarly low SAR. This work urgently needs verification and extension.
Introduction
Mammalian Blood-Brain Barrier
The blood brain barrier in the choroid plexus separates the brain and cerebal spinal fluid of the central nervous system from the blood (and potential blood-borne toxins or micro-organisms). The barrier consists of specialised capillaries, the cells of which form "tight junctions" in an essentially continuous layer. In contrast to most other capillaries in the body those in the cranial vault lack intracellular fenestrae that allow passage of small molecules from blood to the interstitial fluid. The pinocytotic vesicles that transport large molecules across capillaries in peripheral organs are also rare in the capillaries in the brain.
Functionally, the blood-brain barrier is a selectively permeable hydrophobic membrane that allows the passage of small lipid-soluble molecules. Lipid-insoluble substances encounter regulatory interfaces between the blood and the Central Nervous System that control their transport. Certain lipid-insoluble molecules, such as glucose, cross the membrane via carrier proteins.
Electrophysiological Responses
Since the central nervous system co-ordinates and controls an organism's responses to its environment through autonomic and voluntary movements and neurohumoral function, any effect of radiofrequency radiation is important. The reaction of the central nervous system to microwaves may provide evidence of early disturbance in regulatory function of many systems. For instance, the hypothalamus of the forebrain controls thermoregulation and secretion of hormones, while the hippocampus serves behavioural functions such as memory and emotion. Information is generally passed from one neuron to another via the release of neurotransmitter chemicals, such as acetylcholine, dopamine, serotonin, Þ- a m i n o - b u t y r i c - a c i d ( G A B A ) o r e n d o g e n o u s o p i o d s . B i n d i n g of t h e n e u r o t r a n s m i t t e r t o a r e c e p t o r t r i g g e r s a s e r i e s o f r e a c t i o n s t h a t a f f e c t t h e p o s t - s y n a p t i c c e l l . M a n y d r u g s e x e r t t h e i r e f f e c t s b y b i n d i n g t o t h e r e c e p t o r s . T h o s e w h i c h a c t i v a t e t h e r e c e p tor are known as agonists while those which block the action of the endogenous neurotransmitters are antagonists. Since changes in receptor properties can last for many days an animal's normal physiological functions can be altered by any interference in the neurotransmission pathway.
Experimental Evidence
8.1. Blood Brain Barrier
Initial work suggested that exposure to low level pulsed microwave radiation significantly affected blood-brain barrier permeability. Later workers attempted to confirm and extend these observations. The subject has been previously reviewed (Blackwell & Saunders 1986; NCRP 1986). However, the interpretation of the results is difficult; some of the evidence is contradictory and many of the results may well have been confounded by various factors such as the use of anaesthesia or the difficulty in either removing or estimating the amount of tracer. The effects of microwave radiation on the permeability of the blood-brain barrier have been investigated by tracing the penetration, after intravenous injection, of labelled compounds such as protein-bound dyes (fluorescein), radiolabelled saccharides, or horseradish peroxidase. Frey et al (1975) reported the penetration by fluorescein in anaesthetised rats after irradiation at low levels (SAR _ 0.04 - 0.5 W/kg) of pulsed or continuous microwave radiation. In a replication of this study (Merritt et al 1978) and another that exposed conscious rats to 2.45 GHz radiation (Williams et al 1984) at up to 13 W/kg the fluorescein content in brain tissue was found to increase with increasing microwave exposure and brain temperature. However, a decrease in renal clearance of fluorescein was also observed in animals which were hyperthermic (greater than 41°C) suggesting that this may have accounted for the elevation of brain tissue values. The same exposure produced opposite results on the transport of horseradish peroxidase across blood vessel endothelial cells in the brain tissue in conscious animals (Williams et al 1984). The histological assay is less susceptible to artefacts than measurement of fluctuating plasma levels, but is more difficult to quantify. An increase in peroxidase uptake was reported in conscious Chinese hamsters exposed for 2 or 8 h to 100 W/m2 (SAR estimated approx 2 - 3 W/kg) at 2.45 GHz. This effect was confirmed and shown to be reversible (Albert & Kerns 1981).
A number of authors have looked at the uptake into brain tissue of radiolabelled saccharides. The exposure of anaesthetised rats for 20 min to low levels (3 - 20 W/m2; SARs estimated to be 0.06 - 0.4 W/kg) of pulsed 1.3 GHz microwave radiation was reported to increase significantly the permeability of the blood-brain barrier to 14C-labelled saccharides compared to the permeability to 3H-labelled water. However, when brain tissue concentrations of 14C-labelled saccharides were compared to circulating plasma levels in exposed and sham-exposed animals no change in the uptake of sucrose or inulin in the brain tissue was found in anaesthetised rats exposed to continuous or pulsed 1.7 GHz radiation at an SAR of 0.1 W/kg (Ward & Ali 1985). Previous experiments reported a decrease in the uptake of sucrose into the brain tissue of anaesthetised and conscious rats exposed for up to 90 min, to 2.45 GHz radiation at SARs of 0.1 - 13 W/kg. Microwave exposure at SARs up to 6 W/kg increased permeability to sucrose but not inulin in anaesthetised rats, while sucrose permeability in conscious rats was unaffected by microwave exposure (NRPB 1993).
In a study on the effects of MRI exposure on the blood-brain barrier of the rat Salford et al (1992) reported leakage of Evans-blue stained proteins. In a subsequent study using unanaesthetised rats exposed to 915 MHz c.w. or pulsed (modulated at 200, 50, 16 or 8 Hz) they reported passage of albumin across the blood-brain barrier (Salford et al 1993). There was no significant difference between c.w. and pulsed exposures. Dosimetry information was sparse but it appears that the extravasation effect was observed to a varying extent at SAR from 0.33 to 3.3 W/kg.
8.2 Electrophysiological Responses
Changes in the function of nervous tissue, measured electrophysiologically, have been reported during or after whole-body or localised irradiation. These studies are prone to measurement artefact since the use of metallic recording electrodes can greatly perturb the applied field, causing enhanced energy absorption, and there is a chance of field-induced pickup in the leads and electrodes.
High levels of microwave exposure have produced decreases in the latency of evoked potentials recorded during exposure. Johnson and Guy (1972) exposed the heads of cats to 918 MHz radiation for 15 min at 10 - 400 W/m2 and recorded decreased latency in the evoked potentials in the thalamus above a SAR threshold of 2.5 - 5 W/kg. Similar responses were also achieved by conventional heating of the thalamus, and microwave-induced effects could be prevented or reversed with concurrent brain cooling (NRPB 1993).
A series of well-conducted experiments by Lai and colleagues (Lai et al 1984, 1987, 1988, 1989) has shown that exposure to low level pulsed and continuous microwave radiation can act as a non-specific stressor. The acute exposure of rats to pulsed 2.45 GHz radiation (2 µs pulses at 500 pps) at 10 W/m2 (a whole-body average SAR 0.6 W/kg, with a peak SAR of 600 W/kg) was shown to affect the activity of cholinergic neurons in the forebrain. The threshold was reported as 0.45 W/kg, corresponding to a specific energy per pulse of 0.9 mJ/kg (Lai et al 1989). The relative effectiveness of pulsed and continuous microwave radiation at a whole-body SAR of 0.6 W/kg varied in different regions of the brain (Lai et al 1988). Rats exposed for 45 min immediately before daily training sessions in a radial arm maze showed delayed learning performance (Lai et al 1988, 1989).
The radial-arm maze test was used to demonstrate impaired short-term memory function following an acute exposure of 45 min to 2.45 GHz RF at power density of 1 mW/cm2 and estimated whole body SAR 0.6 W/kg. The mechanism of effect has been proposed as one of activation of endogenous opiods in the brain resulting in decreased cholinergic activity in the hippocampus (learning centre). In addition, DNA in brain cells was reported to be damaged, assayed by electrophoretic techniques following a single 45 min exposure (Lai, private communication). The effects were observed with both pulsed (2µs, 500 pps) and c.w. waveforms. Breakage of DNA in the CNS and testes has also been reported recently (Sarka et al 1994) using the same sensitive electrophoretic technique, following exposure to microwaves at 1.18 W/kg SAR.
It is vital that these studies are verified by independent laboratories. The induced changes to neural DNA are unexpected, particularly at the exposure levels used in these studies.
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