Contributions of Hearing Loss and Traumatic Brain Injury to Blast-Induced Cortical Parvalbumin Neuron Loss and Auditory Processing Deficits

Masri, Samer; Deng, Di; Luo, Hao; Zhang, Jinsheng; Bao, Shaowen

doi:10.1089/neu.2022.0179

Cited by 1 publication

(3 citation statements)

References 66 publications

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“…Our results also demonstrate an increase in percentage area stained in all cortical regions other than the RSC at 3-months post-injury, indicating hypertrophy and potentially a change in phenotype. This result aligns with other acute time point studies of blast (Huber et al 2016), and mild blast TBI studies that see both inflammatory responses at later time points (De Lanerolle et al 2011;Goldstein et al 2012;Masri et al 2022;Ou et al 2022). Finally, our results show that there was no significant increase in astrocytic activation at any time point after injury, thus suggesting no obvious astrocyte influence on the electrophysiological changes seen in our study.…”

Section: Discussionsupporting

confidence: 92%

“…As with SST density, a decrease in immunopositively stained PV interneurons can indicate either PV interneuron loss or a reduction in the density of PV by these neurons (Filice et al 2016). In this single blast model of mild TBI, only PV interneurons in the primary auditory cortex were affected, but this might be a result of hearing impairment or loss rather than the blast itself (Masri et al 2022). This could be the case in our model since no ear protection was used in our experimental setup and could have led to temporary hearing loss due to eardrum rupture.…”

Section: Discussionmentioning

confidence: 98%

“…As a result, a lack of change in NeuN staining possibly only reflects the gross impact of blast on all neurons in a region. To counter this potential limitation of NeuN staining, we separately evaluated the neuronal density of two of the most abundant interneuron subtypes in the brain, PV and SST, which have been repeatedly implicated in TBI pathology (Cantu et al 2015; Vascak et al 2018; Masri et al 2022; Frankowski et al 2022). It has been further demonstrated that PV interneuron populations appear to be more vulnerable to nonblast induced TBI than SST interneurons (Nichols et al 2018).…”

Section: Discussionmentioning

confidence: 99%

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Mild blast TBI raises gamma connectivity, EEG power, and reduces GABA interneuron density

May,

Tsikonofilos,

Donat

et al. 2023

Preprint

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At least one traumatic brain injury (TBI) will be experienced by approximately 50-60 million of the world’s population in their lifetime and is the biggest cause of death and disability in those under 40. Mild traumatic brain injury (mTBI) can induce subtle changes but have long-lasting effects that may be difficult to detect through conventional neurological assessment, including standard clinical imaging techniques. These changes can lead to an increased risk of future neurodegeneration and emphasises the need to use more sensitive diagnostic tools such as EEG in order to identify injury and opportunities for therapeutic intervention.In this study, we investigated electrophysiological and histopathological changes in a rat model of mild blast-induced TBI. We used a 32-channel EEG electrode array to detect global and local changes in neural activity and functional connectivity in acute (3 to 4-hours) as well as chronic phases (1 and 3-months) post-injury. GABAergic inhibitory interneurons, crucial for maintaining an excitatory/inhibitory balance, were quantified using immunohistochemistry.Mild blast-induced TBI had minimal effects on resting power and connectivity at the acute timepoint but resulted in resting-state global power increases at all frequencies as well as a relative power increase in slow-wave frequencies in the chronic phase post-injury. Functional connectivity increases in the gamma frequency along with increases in power in the chronic phase pointed towards an alteration in the excitatory/inhibitory balance. Indeed, electrophysiological changes were associated with reduced density of GABAergic interneurons at 7-days, 1-month, and 3months post-injury, with a decrease in somatostatin-positive cell density in the 5th layer of all cortical regions of interest, and a parvalbumin decrease in the 5thlayer of the primary auditory cortex. In contrast, the total number of neurons, measured by NeuN did not change significantly, thus demonstrating a biased impact on inhibitory interneuron populations.Our work demonstrates that the techniques and metrics of injury assessment employed in this study are sensitive enough to reflect the subtle changes present in mTBI and therefore hold potential clinical relevance. By using non-invasive EEG assessments and histopathology, we were able to reveal direct correlates and potential sources of the abnormalities caused by mild blast-induced TBI.

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