Proteomic analysis identifies plasma correlates of remote ischemic conditioning in the context of experimental traumatic brain injury

Maha Saber,Rachel K Rowe,Jonathan Lifshitz,Marissa Mcgilvrey,Patrick Pirrotte,Khyati V Pathak,Krystine Garcia-Mansfield,Jordan L Harrison

doi:10.1038/s41598-020-69865-4

Abstract

Remote ischemic conditioning (RIC), transient restriction and recirculation of blood flow to a limb after traumatic brain injury (TBI), can modify levels of pathology-associated circulating protein. This study sought to identify TBI-induced molecular alterations in plasma and whether RIC would modulate protein and metabolite levels at 24 h after diffuse TBI. Adult male C57BL/6 mice received diffuse TBI by midline fluid percussion or were sham-injured. Mice were assigned to treatment groups 1 h after recovery of righting reflex: sham, TBI, sham RIC, TBI RIC. Nine plasma metabolites were significantly lower post-TBI (six amino acids, two acylcarnitines, one carnosine). RIC intervention returned metabolites to sham levels. Using proteomics analysis, twenty-four putative protein markers for TBI and RIC were identified. After application of Benjamini–Hochberg correction, actin, alpha 1, skeletal muscle (ACTA1) was found to be significantly increased in TBI compared to both sham groups and TBI RIC. Thus, identified metabolites and proteins provide potential biomarkers for TBI and therapeutic RIC in order to monitor disease progression and therapeutic efficacy.

Highlights

Remote ischemic conditioning (RIC), transient restriction and recirculation of blood flow to a limb after traumatic brain injury (TBI), can modify levels of pathology-associated circulating protein
Diffuse TBI suppressed the reflex for a mouse to correct their body position from the supine position
No significant difference in the righting reflex times was observed between TBI and TBI RIC (t(19) = 0.3477, p = 0.7319; Fig. 1B)

Summary

Introduction

Remote ischemic conditioning (RIC), transient restriction and recirculation of blood flow to a limb after traumatic brain injury (TBI), can modify levels of pathology-associated circulating protein. Identified metabolites and proteins provide potential biomarkers for TBI and therapeutic RIC in order to monitor disease progression and therapeutic efficacy. An additional limitation of NSE as a clinical biomarker is the possibility of sample contamination from artifactual hemolysis as a result of collecting or processing blood[16] Though these biomarkers may be helpful for diagnostic measures, these biomarkers are not ideal to monitor disease progression or the effect of treatment. Remote ischemic conditioning (RIC) reduced serum levels of S-100B and NSE 24 h after a severe brain injury when RIC was administered 1 h after hospital a dmission[17]. We hypothesized that RIC would reverse TBIinduced molecular alterations, some of which may serve as biomarkers to monitor recovery

Methods

Results

Conclusion