{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:52Z","timestamp":1760130652838,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PAC 12 athletic association","award":["CAL-Brooks-17-02","R01 AG059715"],"award-info":[{"award-number":["CAL-Brooks-17-02","R01 AG059715"]}]},{"name":"NIH","award":["CAL-Brooks-17-02","R01 AG059715"],"award-info":[{"award-number":["CAL-Brooks-17-02","R01 AG059715"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain injuries (BI) are highly disruptive, often having long lasting effects. Inadequate standard of care (SOC) energy support in the hospital leads to dietary energy deficiencies in BI patients. However, it is unclear how underfeeding (UF) affects protein synthesis post-BI. Therefore, in a rat model, we addressed the issue of UF on the protein fractional synthesis rate (fSR) post-BI. Compared to ad libitum (AL)-fed animals, we found that UF decreased protein synthesis in hind-limb skeletal muscle and cortical mitochondrial and structural proteins (p \u2264 0.05). BI significantly increased protein synthesis in the left and right cortices (p \u2264 0.05), but suppressed protein synthesis in the cerebellum (p \u2264 0.05) as compared to non-injured sham animals. Compared to underfeeding alone, UF in conjunction with BI (UF+BI) caused increased protein synthesis rates in mitochondrial, cytosolic, and whole-tissue proteins of the cortical brain regions. The increased rates of protein synthesis found in the UF+BI group were mitigated by AL feeding, demonstrating that caloric adequacy alleviates the effects of BI on protein dynamics in cortical and cerebellar brain regions. This research provides evidence that underfeeding has a negative impact on brain healing post-BI and that protein reserves in uninjured tissues are mobilized to support cortical tissue repair following BI.<\/jats:p>","DOI":"10.3390\/ijms241713195","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:25:33Z","timestamp":1692951933000},"page":"13195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Underfeeding Alters Brain Tissue Synthesis Rate in a Rat Brain Injury Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-7604","authenticated-orcid":false,"given":"Casey C.","family":"Curl","sequence":"first","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-293X","authenticated-orcid":false,"given":"Robert G.","family":"Leija","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-4960","authenticated-orcid":false,"given":"Jose A.","family":"Arevalo","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam D.","family":"Osmond","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin J.","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Kaufer","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Horning","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1389-1629","authenticated-orcid":false,"given":"George A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of California at Berkeley, Berkeley, CA 94720-3140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref_1","unstructured":"Peterson, A.B., Thomas, K.E., and Zhou, H. (2022). Surveillance Report of Traumatic Brain Injury-Related Deaths by Age Group, Sex, and Mechanism of Injury\u2014United States, 2018 and 2019."},{"key":"ref_2","unstructured":"Peterson, A.B., Xu, L., Daugherty, J., and Breiding, M.J. (2019). Surveillance Report of Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths, United States, 2014."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1089\/neu.2017.5114","article-title":"Imaging of cerebrovascular function in chronic traumatic brain injury","volume":"35","author":"Amyot","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1089\/neu.2010.1512","article-title":"Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion","volume":"31","author":"TalavageThomas","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1093\/brain\/awaa140","article-title":"Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players","volume":"143","author":"Veksler","year":"2020","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1016\/j.clnu.2018.12.035","article-title":"Indirect calorimetry as point of care testing","volume":"38","author":"Rattanachaiwong","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.clnu.2009.04.009","article-title":"Resting energy expenditure in non-ventilated, non-sedated patients recovering from serious traumatic brain injury: Comparison of prediction equations with indirect calorimetry values","volume":"28","author":"McEvoy","year":"2009","journal-title":"Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/00001199-199910000-00007","article-title":"The metabolic response to acute traumatic brain injury and implications for nutritional support","volume":"14","author":"Pepe","year":"1999","journal-title":"J. Head Trauma Rehabil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1089\/neu.2014.3482","article-title":"Endogenous nutritive support after traumatic brain injury: Peripheral lactate production for glucose supply via gluconeogenesis","volume":"32","author":"Glenn","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1089\/neu.2008.0737","article-title":"Metabolic response and nutritional support in traumatic brain injury: Evidence for resistance to renutrition","volume":"26","author":"Charrueau","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00134-004-2489-9","article-title":"Characterization of the alteration of nutritional state in brain injury induced by fluid percussion in rats","volume":"31","author":"Moinard","year":"2005","journal-title":"Intensive Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"71052","DOI":"10.18632\/oncotarget.11958","article-title":"Traumatic brain injury and hyperglycemia, a potentially modifiable risk factor","volume":"7","author":"Shi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00068-016-0724-z","article-title":"The impact of measurement of respiratory quotient by indirect calorimetry on the achievement of nitrogen balance in patients with severe traumatic brain injury","volume":"43","author":"Maxwell","year":"2017","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1097\/TA.0b013e318256de1b","article-title":"A reappraisal of nitrogen requirements for patients with critical illness and trauma","volume":"73","author":"Dickerson","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1089\/neu.2014.3483","article-title":"Lactate: Brain fuel in human traumatic brain injury: A comparison with normal healthy control subjects","volume":"32","author":"Glenn","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrneurol.2010.74","article-title":"Blood\u2013brain barrier breakdown as a therapeutic target in traumatic brain injury","volume":"6","author":"Shlosberg","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7711","DOI":"10.1038\/s41598-017-07394-3","article-title":"TGF\u03b2 signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eaaw8283","DOI":"10.1126\/scitranslmed.aaw8283","article-title":"Blood-brain barrier dysfunction in aging induces hyperactivation of TGF\u03b2 signaling and chronic yet reversible neural dysfunction","volume":"11","author":"Friedman","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Curl, C.C., Kumar, A., Peck, A.J., Arevalo, J.A., Gleason, A., Leija, R.G., Osmond, A.D., Duong, J.J., Miller, B.F., and Horning, M.A. (2022). Fractional Gluconeogenesis: A Biomarker of Dietary Energy Adequacy in a Rat Brain Injury Model. Metabolites, 12.","DOI":"10.3390\/metabo12121163"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0079-6123(08)61984-6","article-title":"Cerebral protein synthesis and ischemia","volume":"63","author":"Bodsch","year":"1985","journal-title":"Prog. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1471-4159.1980.tb07878.x","article-title":"Regional protein synthesis in rat brain following acute hemispheric ischemia","volume":"35","author":"Dienel","year":"1980","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3171\/jns.1991.75.5.0685","article-title":"Cerebral circulation and metabolism after severe traumatic brain injury: The elusive role of ischemia","volume":"75","author":"Bouma","year":"1991","journal-title":"J. Neurosurg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3171\/jns.2005.103.4.0707","article-title":"Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury","volume":"103","author":"Stiefel","year":"2005","journal-title":"J. Neurosurg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/sj.jcbfm.9600073","article-title":"Metabolic crisis without brain ischemia is common after traumatic brain injury: A combined microdialysis and positron emission tomography study","volume":"25","author":"Vespa","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1097\/01.WCB.0000089833.23606.7F","article-title":"Energy dysfunction as a predictor of outcome after moderate or severe head injury: Indices of oxygen, glucose, and lactate metabolism","volume":"23","author":"Glenn","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/ajcn\/2.6.405","article-title":"Nitrogen balance as related to caloric and protein intake in active young men","volume":"2","author":"Calloway","year":"1954","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1021\/jf60067a004","article-title":"Dietary Energy Requirements, Effects of Caloric Intake on Nitrogen Balance and Organ Composition of Adult Rats","volume":"4","author":"Rosenthal","year":"1956","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1113\/JP284967","article-title":"Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females","volume":"601","author":"Oxfeldt","year":"2003","journal-title":"J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E216","DOI":"10.1152\/ajpendo.00545.2007","article-title":"Preserved protein synthesis in the heart in response to acute fasting and chronic food restriction despite reductions in liver and skeletal muscle","volume":"295","author":"Yuan","year":"2008","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1093\/jn\/114.11.2107","article-title":"Nitrogen balance in men with adequate and deficient energy intake at three levels of work","volume":"114","author":"Todd","year":"1984","journal-title":"J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.plrev.2014.03.005","article-title":"Understanding brain networks and brain organization","volume":"11","author":"Pessoa","year":"2014","journal-title":"Phys. Life Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1146\/annurev.neuro.27.070203.144216","article-title":"The plastic human brain cortex","volume":"28","author":"Amedi","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10625","DOI":"10.1073\/pnas.91.22.10625","article-title":"Glutamate uptake into astrocytes stimulates aerobic glycolysis: A mechanism coupling neuronal activity to glucose utilization","volume":"91","author":"Pellerin","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/sj.jcbfm.9600174","article-title":"Lactate: The ultimate cerebral oxidative energy substrate?","volume":"26","author":"Schurr","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1249\/00005768-198606000-00019","article-title":"The lactate shuttle during exercise and recovery","volume":"18","author":"Brooks","year":"1986","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1113\/JP280955","article-title":"Lactate in contemporary biology: A phoenix risen 1","volume":"600","author":"Brooks","year":"2022","journal-title":"J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The science and translation of lactate shuttle theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000017324","article-title":"Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle","volume":"20","author":"Pellerin","year":"1998","journal-title":"Dev. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/jcbfm.2011.149","article-title":"Sweet sixteen for ANLS","volume":"32","author":"Pellerin","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1159\/000094170","article-title":"Induction of monocarboxylate transporter 2 expression and ketone transport following traumatic brain injury in juvenile and adult rats","volume":"28","author":"Prins","year":"2006","journal-title":"Dev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/gerona\/glz069","article-title":"Brain protein synthesis rates in the UM-HET3 mouse following treatment with rapamycin or rapamycin with metformin","volume":"75","author":"Reid","year":"2020","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1152\/japplphysiol.00855.2019","article-title":"CORP: The use of deuterated water for the measurement of protein synthesis","volume":"128","author":"Miller","year":"2020","journal-title":"J. Appl. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1088\/1361-6560\/aa52ad","article-title":"First in vivo traumatic brain injury imaging via magnetic particle imaging","volume":"62","author":"Orendorff","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"zqab028","DOI":"10.1093\/function\/zqab028","article-title":"A novel stable isotope approach demonstrates surprising degree of age-related decline in skeletal muscle collagen proteostasis","volume":"2","author":"Abbott","year":"2021","journal-title":"Function"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1164\/ajrccm.151.6.7767529","article-title":"Cyclosporine A decreases rat skeletal muscle mitochondrial respiration in vitro","volume":"151","author":"Hokanson","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1474-9726.2011.00769.x","article-title":"A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction","volume":"11","author":"Miller","year":"2012","journal-title":"Aging Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E1146","DOI":"10.1152\/ajpendo.1999.276.6.E1146","article-title":"Mass isotopomer distribution analysis at eight years: Theoretical, analytic, and experimental considerations","volume":"276","author":"Hellerstein","year":"1999","journal-title":"Am. J. Physiol.-Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:38:44Z","timestamp":1760128724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,25]]},"references-count":47,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713195"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713195","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,8,25]]}}}