title: Aging with a traumatic brain injury: Could behavioral morbidities and endocrine symptoms be influenced by microglial priming?
abstract: A myriad of factors influence the developmental and aging process and impact health and life span. Mounting evidence indicates that brain injury, even moderate injury, can lead to lifetime of physical and mental health symptoms. Therefore, the purpose of this mini-review is to discuss how recovery from traumatic brain injury (TBI) depends on age-at-injury and how aging with a TBI affects long-term recovery. TBI initiates pathophysiological processes that dismantle circuits in the brain. In response, reparative and restorative processes reorganize circuits to overcome the injury-induced damage. The extent of circuit dismantling and subsequent reorganization depends as much on the initial injury parameters as other contributing factors, such as genetics and age. Age-at-injury influences the way the brain is able to repair itself, as a result of developmental status, extent of cellular senescence, and injury-induced inflammation. Moreover, endocrine dysfunction can occur with TBI. Depending on the age of the individual at the time of injury, endocrine dysfunction may disrupt growth, puberty, influence social behaviors, and possibly alter the inflammatory response. In turn, activation of microglia, the brain's immune cells, after injury may continue to fuel endocrine dysfunction. With age, the immune system develops and microglia become primed to subsequent challenges. Sustained inflammation and microglial activation can continue for weeks to months post-injury. This prolonged inflammation can influence developmental processes, behavioral performance and age-related decline. Overall, brain injury may influence the aging process and expedite glial and neuronal alterations that impact mental health.
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia; Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA. Electronic address: jenna.ziebell@utas.edu.au.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Ziebell
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; Neuroscience Graduate Program, Arizona State University, Tempe, AZ, USA.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Rowe
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Muccigrosso
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; University of Bath, Department of Biology and Biochemistry, Bath, United Kingdom.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Reddaway
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; University of Bath, Department of Biology and Biochemistry, Bath, United Kingdom.
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH, USA; Center for Brain and Spinal Cord Repair, Ohio State University, Columbus, OH, USA; Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Godbout
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; Neuroscience Graduate Program, Arizona State University, Tempe, AZ, USA; VA Healthcare System, Phoenix, AZ, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lifshitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology*; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000473:pathology* / Q000523:psychology*; D004700:Endocrine System Diseases / Q000473:pathology* / Q000523:psychology*; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000523:psychology; D017628:Microglia / Q000473:pathology*
keywords: Aging; Cognition; Endocrine dysfunction; Inflammation; Microglia; Traumatic brain injury