Effect of Fasting Diet on Anxiety and Neuroinflammation in Traumatic Brain Injury

Purpose: Our goal in this project is to investigate the effects of administering an intervention for traumatic brain injury (TBI) through time restricted feeding (TRF) to prevent or interrupt the pathophysiology post-injury and/or enhance the neuroprotective mechanisms after TBI. In addition, a second goal is to identify the mechanism of diet modifications by utilizing next-generation RNA sequencing. We hypothesize that because of the reported neuroprotective benefits of TRF, notably with a meliorating inflammatory responses to disease or injury, that there will be improved neurobehavioral outcomes, specifically a decrease in anxiety after mTBI.

Design: Prospective, mixed subjects, randomized experimental design.

Methods: Mild TBI (mTBI) induced by closed head controlled cortical impact injury (CHI) on rats. Anxiety and locomotion behaviors tested at 24 hours and 1 week post TBI via elevated plus maze (EPM). Total RNA isolated from rat brain tissue used for cDNA libraries. Sample libraries pooled and sequenced on HiSeq 3000 System (Illumina) to produce molecular data from high-throughput sequencing.

Analysis: For this factorial design, multivariate analysis of variance (MANOVA) will be used to determine if TRF has any effect on outcomes measured on the EPM after CHI. Analysis of covariance (ANCOVA) will be used to analyze data pre and post-intervention with the assumption of homogeneity of variance between and within respective groups as well as homogeneity of regression slopes. Molecular data produced were used as input for analysis using R Studio software packages to include DESeq2 (version 1.6.3), Consensus Cluster Plus, KEGG, GAGE, and PathView in order to establish differential gene expression (DEG), unsupervised clustering, and gene ontology.

Implications for Military Nursing: These findings provide potential to improve patient care through the incorporation and improvement associated with “Prolonged Field Care.” Modifications to dietary regimens may possibly unique and straightforward nursing intervention that could be administered as part of prolonged field care associated with combat casualties.