MicroRNA Profile Changes in Brain, Cerebrospinal Fluid, and Blood Following Low-Level Repeated Blast Exposure in a Rat Model.

Abstract

It is well documented that service members are exposed to repeated low-level blast overpressure during training with heavy weapons such as artillery, mortars and explosive breaching. Often, acute symptoms associated with these exposures are transient but cumulative effect of low-level repeated blast exposures (RBEs) can include persistent deficits in cognitive and behavioral health. Thus far, reliable diagnostic biomarkers which can guide countermeasure strategies have not been identified. In this study, rats were exposed to multiple field-relevant blast waves with 8.5 and 10 psi peak positive overpressures, applying one exposure per day for 14 consecutive days. micro-RNAs that can potentially be used as biomarkers for RBEs were assessed in blood, brain, and cerebrospinal fluid (CSF). RBE caused a differential pattern of changes in various miRNAs in blood, brain and CSF in an overpressure-dependent manner. Our key outcomes were decrease of mir-6215 and let-7 family miRNAs and increase of mir-6321 and mir-222-5p in brain, blood, and CSF. Expression pattern of these miRNAs is in concurrence with various neurological conditions such as upregulation of mir-6321 in focal ischemic injury and downregulation of mir-6215 in nerve injury model. Contrarily, Let-7 family miRNAs have neuroprotective role and their downregulation suggests progression of blast induced traumatic brain injury (bTBI) with RBE at 14× -8.5 psi. Repeated blast caused alterations in miRNAs that are likely involved in vascular integrity, inflammation, and cell death. These results indicate that miRNAs are differentially dysregulated in response to blast injuries and may represent better prognostic and diagnostic biomarkers than traditional molecules to identify blast-specific brain injury.