title: Traumatic brain injury and obesity induce persistent central insulin resistance.
abstract: Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.
authors.affiliation: Department of Neuroscience, Center for Brain and Spinal Cord Repair and Group in Behavioral Neuroendocrinology, The Ohio State University Wexner Medical Center, Biomedical Research Tower #618, 460 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Karelina
authors.affiliation: Department of Neuroscience, Center for Brain and Spinal Cord Repair and Group in Behavioral Neuroendocrinology, The Ohio State University Wexner Medical Center, Biomedical Research Tower #618, 460 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sarac
authors.affiliation: Department of Neuroscience, Center for Brain and Spinal Cord Repair and Group in Behavioral Neuroendocrinology, The Ohio State University Wexner Medical Center, Biomedical Research Tower #618, 460 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Freeman
authors.affiliation: Department of Neuroscience, Center for Brain and Spinal Cord Repair and Group in Behavioral Neuroendocrinology, The Ohio State University Wexner Medical Center, Biomedical Research Tower #618, 460 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Kristopher R
authors.initials: KR
authors.lastname: Gaier
authors.affiliation: Department of Neuroscience, Center for Brain and Spinal Cord Repair and Group in Behavioral Neuroendocrinology, The Ohio State University Wexner Medical Center, Biomedical Research Tower #618, 460 West 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weil
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007858:Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt
keywords: anxiety; central metabolism; high-fat diet; insulin receptor; mouse; neuroinflammation