Acute and sub-acute microRNA dysregulation is associated with cytokine responses in the rodent model of penetrating ballistic-like brain injury.

Background: MicroRNAs (miRNAs) are small stable RNAs that regulate translational degradation or repression of genes involved in brain trauma-mediated inflammation. More recently, miRNAs have emerged as potential novel TBI biomarkers. The aim of this study was to determine if a select set of miRNAs (miR-21, Let-7i, miR-124a, miR-146a, miR-107) that were previously associated with TBI models and clinical studies would be dysregulated and correlated to inflammatory cytokine abundance in the rat penetrating ballistic-like brain injury (PBBI) model. Methods: Adult male Sprague-Dawley rats received a unilateral frontal 10% PBBI, which produces a temporary cavity. Sham animals received a craniotomy only. Ipsilateral brain tissue and serum were collected 4h-7d post-injury. Quantitation of miR-21, Let-7i, miR-124a, miR-146a, or miR-107 levels was conducted using Taqman PCR assays normalized to the endogenous reference, U6 snRNA. Brain tissue derived from matching cohorts was used to determine 1L-1beta and IL6 levels by ELISA. Results: Brain tissue Let-7i and miR-21 increased at 4h and 1d, while miR-124a and miR-107 were enhanced only 1d post-injury. MiR-146a displayed a bi-phasic response and increased 1d and 7d, whereas elevation of miR-21 was sustained 1-7d after PBBI. Pathway analysis indicated that miRNAs were linked to inflammatory proteins, IL-6 and IL-1beta. Confirmation by ELISA indicated that both cytokines were increased and peaked at 1d, but fell at 3-7d after PBBI indicating an inverse relationship with miRNA abundance. Serum Let-7i, alone, was differentially abundant 7d after PBBI. Conclusions: Brain tissue derived miRNAs linked to increased cytokine levels demonstrates a plausible therapeutic target of TBI induced-inflammation. Suppression of serum derived Let-7i may have utility as a biomarker of subacute injury progression or therapeutic responses. (C) 2017 Lippincott Williams & Wilkins, Inc.

from Emergency Medicine via xlomafota13 on Inoreader http://ift.tt/2pHgp1E