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

Abstract

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 4 hours to 7 days 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 IL-6 levels by enzyme-linked immunosorbent assay.

RESULTS:

Brain tissue Let-7i and miR-21 increased at 4 hours and 1 day, whereas miR-124a and miR-107 were enhanced only 1 day post-injury. MiR-146a displayed a biphasic response and increased 1 day and 7 days, whereas elevation of miR-21 was sustained 1 day to 7 days after PBBI. Pathway analysis indicated that miRNAs were linked to inflammatory proteins, IL-6 and IL-1beta. Confirmation by enzyme-linked immunosorbent assay indicated that both cytokines were increased and peaked at 1 day, but fell at 3 days through 7 days after PBBI, indicating an inverse relationship with miRNA abundance. Serum Let-7i, alone, was differentially abundant 7 days after PBBI.

CONCLUSION:

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.

• Authors: David Johnson, Casandra M Cartagena, Frank C Tortella, Jitendra R Dave, Kara E Schmid, Angela M Boutté
• Journal: The journal of trauma and acute care surgery (J Trauma Acute Care Surg) Vol. 83 Issue 1 Suppl 1 Pg. S145-S149 (07 2017) ISSN: 2163-0763 [Electronic] United States
• PMID: 28452880 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• Cytokines
• MicroRNAs

Topics

• Animals
• Biomarkers (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Head Injuries, Penetrating (metabolism)
• Male
• MicroRNAs (metabolism)
• Military Medicine
• Polymerase Chain Reaction
• Rats
• Rats, Sprague-Dawley