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Τρίτη 12 Ιανουαρίου 2021

Neuroprotectin D1 Attenuates Blast Overpressure Induced Reactive Microglial Cells in the Cochlea

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Objective/Hypothesis

We examined a neuroinflammatory response associated with glial activation in the cochlea exposed to blast overpressure and evaluated the potential therapeutic efficacy of specialized pro‐resolving mediators such as neuroprotectin D1, NPD1; (10R, 17S‐dihydroxy‐4Z, 7Z, 11E, 13E, 15Z, 19Z‐docosahexaenoic acid) in a rodent blast‐induced auditory injury model.

Study Design

Animal Research.

Methods

A compressed‐air driven shock tube was used to expose anesthetized adult male Long‐Evan rats to shock waves simulating an open‐field blast exposure. Approximately 30 minutes after blast exposure, rats were treated with NPD1 (100 ng/kg body wt.) or vehicle delivered intravenously via tail vein injection. Rats were then euthanized 48 hours after blast exposure. Unexposed rats were included as controls. Tissue sections containing both middle and inner ear were prepared with hematoxylin–eosin staining to elucidate histopathological changes associated with blast exposure. Cochlear tissues were evaluated for relative expression of ionized calcium‐binding adaptor 1 (Iba1), as an indicator of microglial activation by immunohistochemistry and western blot analyses.

Results

Our animal model resulted in an acute injury mechanism manifested by damage to the tympanic membrane, hemorrhage, infiltration of inflammatory cells, and increased expression of Iba1 protein. Moreover, therapeutic intervention with NPD1 significantly reduced Iba1 expression in the cochlea, suggesting a reduction of a neuroinflammatory response caused by blast overpressure.

Conclusions

Blast overpressure resulted in an increased expression of proteins involved in gliosis within the auditory system, which were reduced by NPD1. Treatment of NPD1 suggests an effective strategy to reduce or halt auditory microglial cell activation due to primary blast exposure.

Level of Evidence

N/A Laryngoscope, 2021

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Δημοσίευση σχολίου

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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