Int. J. Environ. Res. Public Health 2010, 7 3733 These findings demonstrated that the resveratrol anti-oxidant properties can be protective against NIHL, strengthening the hypothesis that noise damage is due to oxidative stress [28]. Another study by the senior author in 2009 [29] investigated the effects of anti-intracellular adhesion molecule-1 antibody (Anti-ICAM-1 Ab) on NIHL. ICAM-1 leads to neutrophil endothelial cell adhesion [30] which can subsequently lead to increased circulating levels of cytokines, leukotrienes, thromboxanes, platelet activating factor, complement components, elastases, and other enzymes, as well as additional formation of ROS [31]. In this study, Fischer rats were randomized into a control group with saline and a treatment group where they received intravenous Anti-ICAM-1 Ab prior to a 72-hour period of 107 dB SPL noise. The groups then received another dose of Anti-ICAM-1 Ab or saline 24 hours after noise exposure. The rats treated with Anti-ICAM-1 Ab showed attenuated temporary threshold shifts (TTS) compared to the control group. This study demonstrated that by using Anti-ICAM-1 Ab to block the cascade of ROS, rats were protected against NIHL, strengthening the evidence of the oxidative stress hypothesis [29]. There have been numerous studies on the role of oxidative stress in hearing loss and the ability of various anti-oxidants to attenuate the physiological damage. Coleman et al. [32] found that N-Acetylcysteine and acetyl-L-carnitine both significantly reduced permanent threshold shifts and hair cell loss in mice compared to saline-treated controls when exposed to a consistent noise. Samson et al. [33] found that the anti-oxidant D-methionine reversed the change in lipid peroxidation and significantly reduced permanent threshold shifts on day 14 from 15 dB to 5 dB at the 4 kHz range in mice. There are many other studies that have investigated the role of anti-oxidants in NIHL and we suggest the reader to look at the cited review articles for more information [21,34,35]. Another hypothesis looked at the role of glutamate in NIHL. Noise exposure is known to cause excessive excitatory synaptic activation of glutamate receptors and leads to glutamate excitotoxicity. This process ultimately results in neural swelling through water and calcium influx, which induces necrotic and apoptotic cell death in the spiral ganglion. This results in permanent mechanical changes and subsequent hearing loss [20,36]. Many of these theories may contribute to the mechanism of NIHL. 3. Physiological Response to Noise Noise can have a more global effect on human physiology and act upon multiple non-auditory systems such as cardiovascular, neuroendocrine, and psychological [37]. Quantifying the non-auditory effects of noise may be difficult due to lack of strong scientific evidence lack statistical evidence, as there are often plausible alternative explanations for the results. These studies often have confounding variables, especially selection bias. There have been multiple studies that have investigated the relationship between noise, blood pressure, and myocardial damage. A comprehensive meta-analysis by van Kempen et al. [38] looked at 43 epidemiological studies looking at the correlation between noise exposure and elevated blood pressure and ischemic heart disease during the time period of 1970 and 1999. They found that there was a significant association between occupational and air-traffic noise exposure and hypertension. The evidence of noise exposure causing ischemic heart disease was inconclusive as there was no definitive relationship.