Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics

• Published in: Cellular and molecular neurobiology Vol. 37; no. 4; pp. 571 - 585
• Main Authors: Pearn, Matthew L., Niesman, Ingrid R., Egawa, Junji, Sawada, Atsushi, Almenar-Queralt, Angels, Shah, Sameer B., Duckworth, Josh L., Head, Brian P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2017; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiopathology; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - physiopathology; Brain Injuries, Traumatic - therapy; Caveolin; Caveolin-1; Caveolins - metabolism; Cell Biology; Disease Models, Animal; Etiology; Extravasation; Gene therapy; Hemorrhage; Homeostasis; Humans; Inflammation; Inflammation - drug therapy; Leakage; Lipid rafts; Magnetic fields; Neurobiology; Neurosciences; Neurotransmitters; Neurotrophic factors; Review Paper; Stem cells; Structure-function relationships; Traumatic brain injury; Treatment Outcome; Wounds; Neuroinflammation; Traumatic brain injury; Membrane/lipid rafts; Caveolin; Biologics; Blood–brain barrier
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-016-0400-1

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.