Caloric adequacy normalizes brain tissue protein turnover in a rat brain injury model

Abstract

Traumatic brain injury (TBI) is a leading cause for hospitalization in America, often having long lasting effects including increased morbidity, mortality and cognitive deficits post recovery. Based on Standard of Care (SOC) treatment, TBI patients are grossly underfed, yet it is unclear how underfeeding effects protein turnover post-TBI. Thus, we designed a study to elucidate the effects of TBI and caloric restriction (CR) on protein dynamics post-TBI. Hypothesis: We hypothesize that TBI would elicit an increased fractional synthesis rate (FSR) in all brain tissue as compared to control, ad libitum (AL) fed animals, while CR would suppress FSR. Thus, we predicted that the CR+TBI animals would have an elevated FSR over CR control but suppressed compared to AL+TBI animals. Methods: Deuterium oxide was used to measure FSR 13-day post TBI in multiple tissues [skeletal muscle, heart, right and left cerebellum, right and left cortex and hippocampus] of Sprague Dawley rats, AL fed control (AL-Con: n=3), AL+TBI (n=6), or CR+TBI (n=5) and CR-Control (n=6). Tissue homogenates were fractionated to isolate the mitochondrial fraction, and cytoplasmic/sarcoplasmic fraction. Pentafluorobenzyl bromide derivatized alanine samples were measured by GC-MS to evaluate ions with m/z 448, 449, 450. FSR was determined using the m/z ion ratios and MIDA. We found that TBI significantly increased FSR over control animals in the left and right cortex (p≤0.05) and suppressed FSR in the cerebellum (p≤0.05). We found that CR in conjunction with TBI caused an increased FSR in the mitochondrial, cytosolic, and whole tissue of the cortical regions of the brain compared to CR control animals (p≤0.05). The increased FSR found with the CR-TBI group was mitigated with ad lib feeding, exhibiting caloric adequacy mitigates the effects of TBI in cortical and cerebral brain regions. This research shows evidence that caloric restriction has a negative impact on brain healing post-TBI. This project was funded by a grant to GAB from the PAC 12 athletic association (CAL-Brooks-17-02) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.