Abstract
Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.
Highlights
Our results showed that that blast exposure significantly elevated manganese accumulation in rats with tinnitus behavior in a bilateral fashion compared to control rats, manganese accumulation was not greater in tinnitus(+) versus tinnitus(−) rats
On a group level, repeated measures ANOVA showed that tinnitus(+) rats exhibited a significant interaction between time and frequency (F(5,27) = 5.798, p < 0.001)
For prepulse inhibition (PPI) ratio data (Fig. 1b), repeated measures ANOVA showed no significant effect of time (F(1,31) = 1.833, p = 0.186) or interaction between time and frequency (F(5,27) = 0.931, p = 0.477), indicating that auditory detection was not impaired and did not confound gap-detection deficits
Summary
In tinnitus patients have shown abnormal sound-evoked activity in the cochlear nuclei and inferior colliculi[15,16,17,18,19], as well as abnormal brain metabolism[20,21,22,23,24,25,26], and alterations in microstructural integrity[27,28,29,30,31,32] and gray matter volume[33,34,35]. MEMRI studies on animals with tinnitus have found increased manganese accumulation, or activity, in the DCN, ventral cochlear nucleus (VCN), IC, and paraflocculus[59,60,61,62]. Five weeks following blast exposure, we performed Morris water maze (MWM) and elevated plus maze (EPM) testing to assess spatial cognition and anxiety, respectively. This was followed by MEMRI to study the effect of blast-induced tinnitus and its associated TBI on activation of the central auditory and limbic systems. Our data suggests that blast-induced tinnitus may play a role in brain activation, but the non-auditory effects of blast and potentially-induced TBI must be considered
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