**5. Conclusions**

*Acoustics of Materials*

impairment [53].

mate release [54].

against infrasound-induced injury [55].

TRPV4 were increased as compared to non-exposed controls. Pharmacological or knock-out intervention of TRPV4 in cultured glial cells decreased the levels of inflammatory cytokines and attenuated neuronal apoptosis. This study also demonstrated the involvement of calmodulin and protein kinase C signaling pathways in the response to infrasonic exposures. These data suggest that TRPV4 expressed by glial cells is potentially a key factor in infrasound-induced neuronal

Neonatal rat hippocampal astrocyte cultures were exposed to 16 Hz at 130 dB for 15, 30, 60, 90, 120, and 240 minutes. Extra-cellular glutamate levels increased with increasing exposure time, and at 90 min, there was a 100% increase over baseline. The astroglial expression of Cx43 (connexin43—see above) was increased, as compared to non-exposed controls, as was the synthesis of Cx43 mRNA. Through additional evaluations using pharmacological and knock-out interventions, the authors concluded that infrasonic exposures induced astrocytes to release glutamate, and that Cx43 gap junctions were required for the exposure-induced gluta-

The endocannabinoid system includes lipid-based retrograde neurotransmitters, expressed throughout the CNS, and involved in fertility, pregnancy, pre-and postnatal development, appetite, pain-sensation, mood, and memory. Animals were exposed to 16 Hz at 130 dB, 2 hours daily, for 14 days. Cannabinoid (CB) receptors 1 and 2 in the CA1 hippocampal region of the exposed rats were downregulated in a time-dependent manner, as compared to non-exposed controls. Apoptotic cells in the CA1 only became obvious after day 5, and cell death coincided with the decreased expression of CB receptors. Through pharmacological intervention, activation of CB receptors significantly reduced the number of apoptotic cells, ameliorated the behavior performance of exposed rats, and reduced the infrasound-elevated levels of proinflammatory cytokines. These data suggest that CB receptors could potentially serve as promising targets for future treatments

Fibroblasts synthesize extracellular matrix (glycosaminoglycans, reticular, and elastic fibers) and collagen, and, in addition to their structural role, fibroblasts are also important for mounting the immune response to tissue damage. Fibroblast growth factors (FGF) signal through fibroblast growth factor receptors (FGFR). The fibroblast growth factor 2/fibroblast growth factor receptor 1 (FGF2/FGFR1) signaling pathway was investigated in animals and in cultured astrocytes, exposed to 16 Hz at 150 dB, 2 hours daily, for 1, 3, or 7 days. In both experimental models, astrocyte activation increased with exposure time and astrocyte-expressed FGFR1 was downregulated as compared to non-exposed controls. Pharmacological intervention using FGF2 exerted an inhibitory effect on infrasound-induced astrocyte activation, inhibited the elevation of proinflammatory cytokines, upregulated the expression of FGFR1, and alleviated neuron loss in CA1 hippocampus region. Inhibition of the FGF2/FGFR1 pathway aggravated astrocyte-mediated inflammation after infrasonic exposure. The authors concluded that astrocyte-mediated inflammation was involved in infrasound-induced neuronal damage and that the FGF2/FGFR1 pathway played

In a laboratory setting, rats were exposed to tonal 8 Hz at 140 dB, 2 hours daily, for 3 days. A post-exposure, 1-week time point was also established. Significant damage of hippocampus morphology was observed in exposed rats, and recovery was seen after 1 week of post-exposure. Neuronal apoptosis was significantly increased after 24- and 48-hour exposures, as compared to non-exposed controls, and then decreased after 1 week post-exposure. Expression of heat shock protein 70

(HSP70) peaked at 24 hours and was decreased at 48 hours [57].

**112**

a key role [56].

Exposure to infrasonic and lower frequency airborne pressure waves can cause cellular and tissue damage depending on frequency, dB-level, and exposure time, while the viscoelastic properties inherent to biological tissues impart a nonlinear response to this type of acoustic stressor. The complex mechanosensitive and biochemical cellular signaling pathways mediating this cellular damage have not yet been pinpointed, although fasciae structures and connective tissues (including the neuroglia) seem to be the most sensitive under longer term exposures. Immediate exposures appear to induce inflammatory processes that do not seem to be maintained with longer exposures.

Widespread vascular involvement (not limited to the biological structures addressed herein) was observed in palpebral and bulbar conjunctiva and retina, gastric mucosa, liver structures, lungs, pleura and tracheae, alveoli, pericardia, and coronary arteries. This vascular response may (unsuspectingly) be the underlying cause of many symptomatic complaints. Cognitive deficits oftentimes documented within residential field laboratories may not merely be due to sleep deprivation, but also to hippocampal neuronal damage. Fasciae morphogenesis speaks to the demand on the whole-body structural integrity elicited by this type of external mechanical insult, while collagenous growths and hemorrhagic events of a focal nature may reflect concomitant resonance phenomena.

Recovery periods are not linear, and 2-hour daily exposures imply a 22-hour nonexposure period. This presents a problem for continuous exposures, such as those encountered in some professional activities and most residential environments. The underlying objectives of most of the studies discussed herein are related to occupational exposures and do not consider continuous exposures at less than 90 dB, nor are pressure pulsed trains presented within the laboratorial acoustic environments. In residential environments, however, these attributes are often present. The simulation of residential exposures does not appear to have yet been integrated into laboratory settings and protocols.

The whole-body response also elicits the immune system, affects organs of the reproductive system, changes receptor cells in the vestibular semicanals and auditory cochlea, and induces genotoxic effects, including teratogenesis. This is a pioneering field of science, still in its infancy and urgently requiring scientists from multidisciplinary areas of study because, ultimately, the health of human populations and their offspring must be protected.
