Research ArticleBlast Exposure Disrupts the Tonotopic Frequency Map in the Primary Auditory Cortex
Graphical abstract
Introduction
Exposure to blast shockwaves can cause sensory and neurological disorders in the auditory system, such as hearing loss, tinnitus, hyperacusis and central processing disorder (Jury and Flynn, 2001, Rossiter et al., 2006, Sayer et al., 2008, Belanger et al., 2009, Mao et al., 2012, Remenschneider et al., 2014, Saunders et al., 2015, Bressler et al., 2017, Ouyang et al., 2017). However, the mechanism by which blasts impact the auditory system remains unclear (Rosenfeld and Ford, 2010). Exposure to shockwaves causes damage to the ear, but the impact can be quite different from that of noise exposure (Bauer et al., 2008). Blast shockwaves are brief and often rupture the tympanic membrane, which decouples the inner ear from further mechanical over-stimulation (Xydakis et al., 2007). Consequently, blast exposure often causes severe acute hearing loss, but only mild long-term hearing loss following recovery of the tympanic membrane (Mao et al., 2012, Chen et al., 2013, Saunders et al., 2015, Bressler et al., 2017). By contrast, exposure to loud noises typically does not rupture the tympanic membrane, meaning that mechanical over-stimulation of the inner ear can be sustained, potentially resulting in more long-term hearing loss (Yang et al., 2011). Therefore, damage to hair cells, spiral ganglion neurons, and the central auditory pathway resulting from these distinctly different auditory traumas may vary greatly (Luo et al., 2014a, Luo et al., 2014b, Niwa et al., 2016, Luo et al., 2017).
In addition to hearing loss, blasts cause traumatic brain injury (TBI) and may introduce additional pathologies to the central auditory pathway (Kamnaksh et al., 2011, Mao et al., 2012, Valiyaveettil et al., 2012, Tate et al., 2014, Race et al., 2017). Solid body structures, such as the brain, were previously considered to be at low-risk of sustaining shockwave injury (Argyros, 1997, Elsayed, 1997, Stuhmiller, 1997, Cernak et al., 2001). However, subsequent studies have revealed a wide range of cellular injuries and inflammatory responses that occur despite a lack of hemorrhage or gross brain damage (Cernak et al., 2001, Sajja et al., 2012, Abdul-Muneer et al., 2013, Arun et al., 2013). For example, shockwaves from a single blast can compromise the membranes of neural and glial cells, allowing intracellular proteins to leak into cerebrospinal fluid (Saljo et al., 2003, Leung et al., 2008). Likewise, shockwave exposure activates resident microglia and astrocytes within 30 min (Kaur et al., 1995, Cernak et al., 2001, Cernak et al., 2011, Saljo et al., 2001, Svetlov et al., 2010, Du et al., 2017). Activated microglia subsequently release TNF-α and other pro-inflammatory cytokines, generating both acute and chronic cellular inflammatory responses (Garden and Moller, 2006).
Here we examine the effects of blast shockwave exposure on the auditory frequency map in the primary auditory cortex (AI) of the rat. We found that blast exposure resulted in distorted frequency maps with over-representation of seemingly random narrow frequency ranges.
Section snippets
Animals
All procedures used in this study were approved by the Animal Care and Use Committees at the University of Arizona and Wayne State University. Ten Sprague–Daley rats, male and 2-month-old, were purchased from Charles River and used in this study. Five were chosen randomly and assigned to the blast-exposed group and the remaining five rats were assigned to the sham-exposed group.
Blast exposure and behavioral tests
Blast exposure was performed as described before (Mao et al., 2012). The rat was anesthetized with isoflurane (0.75–1%
Results
The cortical frequency map in AI was examined in blast- and sham-exposed animals 3 months after the exposure. AI frequency maps of sham-exposed animals were tonotopically organized, with all frequencies approximately equally represented in each animal (one-sample Kolmogorov–Smirnov’s test against a log-uniform distribution from 2 kHz to 32 kHz, p > 0.1; for example, see Fig. 1, Z-3 and Z-14). By contrast, all blast-exposed animals had a large area in AI that over-represented a relatively narrow
Discussion
In this study we have shown that blast exposure disrupts the AI frequency map and changes neuronal response properties. Some of these changes are similar to those observed in animals following noise exposure. For example, the increased response threshold and shortened response latencies observed in this study have previously been reported following noise exposure (Gallo and Glorig, 1964, Syka and Rybalko, 2000, Norena et al., 2003). Noise exposure often results in hearing loss in a limited
Acknowledgment
The research was supported by Department of Defense (W81XWH-11-2-0031). We thank Alexander K. Zinsmaier for comments on the manuscript.
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2022, Hearing ResearchCitation Excerpt :Shock waves from a single blast can impair the membranous integrity of neural and glial cells, causing intracellular contents to leak into the cerebrospinal fluid. Additionally, activated microglia cells may release pro-inflammatory cytokines, such as TNF-α, which result in significant neuroinflammation (Masri et al., 2018). These pathophysiological changes likely contribute to the widespread degenerative changes observed in many regions of the brain including CAS structures, characterized by axonal swelling, vacuoles, and GFAP reactive astrocytosis (Arun et al., 2021; Du et al., 2013; Kallakuri et al., 2018).
Correlation of Electrophysiological and Gene Transcriptional Dysfunctions in Single Cortical Parvalbumin Neurons After Noise Trauma
2022, NeuroscienceCitation Excerpt :In the neurons that were PV+, the PV protein signal was significantly reduced (Masri et al., 2021). These results are consistent with previous reports of the noise-induced reduction in PV+ neuron density in the auditory cortex (Masri et al., 2018; Deng et al., 2020; Zinsmaier et al., 2020; Masri et al., 2021). The reduction of GAD mRNA levels is consistent with previous reports of reduced GAD protein expression following NIHL (Yang et al., 2011; Masri et al., 2021).
Assessment of auditory and vestibular damage in a mouse model after single and triple blast exposures
2021, Hearing ResearchCitation Excerpt :A limitation of the current work is that we did not evaluate the contribution of blast-induced TBI or neuropathy in the auditory CNS to the hearing loss we observed. Previous work in rats has shown that blast exposure damages the central auditory system (Mao et al., 2012; Sosa et al., 2013; Kallakuri et al., 2018), reduces the sensitivity and spontaneous discharge rates of vestibular afferents (Yu et al., 2020), and can even alter the tonotopic organization of the auditory cortex (Masri et al., 2018). Additional studies are needed to evaluate the relative contributions of peripheral and central damage to auditory and vestibular deficits caused by blast exposure.
Mild traumatic brain injury induced by primary blast overpressure produces dynamic regional changes in [<sup>18</sup>F]FDG uptake
2019, Brain ResearchCitation Excerpt :Recently, it has been demonstrated that blast exposure in mice causes increases in dendritic branching and dendritic spine density in the basolateral amygdala as early as 72 h post-injury (Ratliff et al., 2019), where we observed acute changes in metabolic activity. Additionally, we observed changes in [18F]FDG uptake in auditory cortex as well as inferior colliculus, regions implicated in blast-induced central auditory processing deficits (Mao et al., 2012; Masri et al., 2018; Race et al., 2017). In summary, a number of mechanisms can potentially explain the region-specific nature of altered [18F]FDG uptake following blast injury.