title: Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.
abstract: Traumatic brain injury (TBI) is one of the leading causes of death of young people in the developed world. In the United States alone, 1.7 million traumatic events occur annually accounting for 50,000 deaths. The etiology of TBI includes traffic accidents, falls, gunshot wounds, sports, and combat-related events. TBI severity ranges from mild to severe. TBI can induce subtle changes in molecular signaling, alterations in cellular structure and function, and/or primary tissue injury, such as contusion, hemorrhage, and diffuse axonal injury. TBI results in blood-brain barrier (BBB) damage and leakage, which allows for increased extravasation of immune cells (i.e., increased neuroinflammation). BBB dysfunction and impaired homeostasis contribute to secondary injury that occurs from hours to days to months after the initial trauma. This delayed nature of the secondary injury suggests a potential therapeutic window. The focus of this article is on the (1) pathophysiology of TBI and (2) potential therapies that include biologics (stem cells, gene therapy, peptides), pharmacological (anti-inflammatory, antiepileptic, progrowth), and noninvasive (exercise, transcranial magnetic stimulation). In final, the review briefly discusses membrane/lipid rafts (MLR) and the MLR-associated protein caveolin (Cav). Interventions that increase Cav-1, MLR formation, and MLR recruitment of growth-promoting signaling components may augment the efficacy of pharmacologic agents or already existing endogenous neurotransmitters and neurotrophins that converge upon progrowth signaling cascades resulting in improved neuronal function after injury.
authors.affiliation: Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, VA Medical Center 125, University of California, 3350 La Jolla Village Drive, San Diego, CA, 92161-5085, USA.|Department of Anesthesiology, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Pearn
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.|Sanford Consortium for Regenerative Medicine, La Jolla, San Diego, CA, 92037, USA.
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Niesman
authors.affiliation: Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, VA Medical Center 125, University of California, 3350 La Jolla Village Drive, San Diego, CA, 92161-5085, USA.|Department of Anesthesiology, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: Junji
authors.initials: J
authors.lastname: Egawa
authors.affiliation: Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, VA Medical Center 125, University of California, 3350 La Jolla Village Drive, San Diego, CA, 92161-5085, USA.|Department of Anesthesiology, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawada
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.|Sanford Consortium for Regenerative Medicine, La Jolla, San Diego, CA, 92037, USA.
authors.forename: Angels
authors.initials: A
authors.lastname: Almenar-Queralt
authors.affiliation: UCSD Departments of Orthopaedic Surgery and Bioengineering, University of California, La Jolla, San Diego, CA, 92093, USA.
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
authors.affiliation: Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
authors.forename: Josh L
authors.initials: JL
authors.lastname: Duckworth
authors.affiliation: Department of Anesthesiology, Veterans Affairs San Diego Healthcare System, VA Medical Center 125, University of California, 3350 La Jolla Village Drive, San Diego, CA, 92161-5085, USA. bhead@ucsd.edu.|Department of Anesthesiology, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA. bhead@ucsd.edu.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Head
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D022461:Caveolins / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D022461:Caveolins
keywords: Biologics; Blood–brain barrier; Caveolin; Membrane/lipid rafts; Neuroinflammation; Traumatic brain injury