Time course of blast-induced injury in the rat auditory cortex

Abstract

Blast exposure is an increasingly significant health hazard and can have a range of debilitating effects, including auditory dysfunction and traumatic brain injury. To assist in the development of effective treatments, a greater understanding of the mechanisms of blast-induced auditory damage and dysfunction, especially in the central nervous system, is critical. To elucidate this area, we subjected rats to a unilateral blast exposure at 22 psi, measured their auditory brainstem responses (ABRs), and histologically processed their brains at 1 day, 1 month, and 3-month survival time points. The left and right auditory cortices was assessed for astrocytic reactivity and axonal degenerative changes using glial fibrillary acidic protein immunoreactivity and a silver impregnation technique, respectively. Although only unilateral hearing loss was induced, astrocytosis was bilaterally elevated at 1 month post-blast exposure compared to shams, and showed a positive trend of elevation at 3 months post-blast. Axonal degeneration, on the other hand, appeared to be more robust at 1 day and 3 months post-blast. Interestingly, while ABR threshold shifts recovered by the 1 and 3-month time-points, a positive correlation was observed between rats’ astrocyte counts at 1 month post-blast and their threshold shifts at 1 day post-blast. Taken together, our findings suggest that central auditory damage may have occurred due to biomechanical forces from the blast shockwave, and that different indicators/types of damage may manifest over different timelines.

Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain

“…Since the auditory cortex is the most important brain region involved in auditory signal processing, the rapid cellular senescence in this brain region may have implications concerning the chronic auditory dysfunctions that are widely seen after blast exposures. Preclinical studies have shown acute and chronic neuronal degeneration in the auditory cortex after blast exposure (45). Electrophysiological evaluations of the auditory cortex after blast exposure showed spontaneous firing of neurons up to 3 months post-blast indicative of blastinduced tinnitus (46).…”

MiR-421 Binds to PINK1 and Enhances Neural Stem Cell Self-Renewal via HDAC3-Dependent FOXO3 Activation

“…A total of 140 7-day-old newborn mice, weighing 4.0 ± 0.5 g, were sham-operated ( n = 20) or modeled with IBI followed by transduction of lentiviral vectors carrying plasmids expressing miR-421 mimic alone or in combination with SC97 (4 μg/ml, Selleckchem, Houston, TX, United States), overexpression (oe)-PINK, or oe-PINK + oe-FOXO3, n = 20. The IBI model was established as previously described ( Ten et al, 2003 ; Kallakuri et al, 2018 ). Briefly, all mice were housed under controlled conditions of temperature (24°C), with free access to food.…”

Blast Exposure Causes Long-Term Degeneration of Neuronal Cytoskeletal Elements in the Cochlear Nucleus: A Potential Mechanism for Chronic Auditory Dysfunctions

“…On the right side, silver-stain densities for sham controls and single and repeated blast-exposed animals were 36.57 ± 6.09, 34.48 ± 5. 16…”

“…Genomic analysis of the inner ear samples on days 1 and 28 post-blast exposures revealed differential expression of several genes involved in mechanotransduction, cytoskeletal reorganization, myelin development, and axon survival ( 9 ). Few preclinical studies have explored the acute and subacute changes in auditory signal processing centers in the brain after blast exposure ( 13 , 16 , 17 ). In the present study, we have evaluated the effect of single and repeated blasts on neuronal degeneration in the brain regions involved in auditory signal processing in rats to determine whether blast exposure can cause acute and chronic CASPD.…”