Modeling the pathobiology of repetitive traumatic brain injury in immortalized neuronal cell lines.
Repetitive mild traumatic brain injury (mTBI) represents a major public health problem. Many individuals who suffer repetitive mTBIs suffer from Post-Concussion Syndrome, a constellation of neuropsychiatric symptoms that includes depression, anxiety, and problems with memory and other cognitive processes. Significantly, Post-Concussion Syndrome is resistant to existing therapeutic strategies. To provide better treatment options for this patient population, the underlying pathophysiology of repetitive mTBI must be understood. A first step in this process is the establishment of an in vitro model system that recapitulates the biological changes that occur in the brains of repetitively injured humans. The availability of a model with immortalized cell lines would remove the considerable barriers of time, expense, and difficulties with genetic manipulation that exist with the use of primary neuronal cultures. Here we report the development and functional characterization of an in vitro laboratory model of repetitive TBI using immortalized neuronal cell lines. These results indicate that the moderate, repetitive injury reduces viability, numbers and lengths of neurites, and that the neuronal loss mechanism includes caspase activation.
Laboratory of Molecular Biology, Research and Development 151, Bay Pines VA Healthcare System, Bay Pines, FL 33744, USA.
Michael J
MJ
Kane
Haris
H
Hatic
Vedad
V
Delic
John S
JS
Dennis
Carrie L
CL
Butler
Jessica N
JN
Saykally
Bruce A
BA
Citron
D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D016501:Neurites / Q000201:enzymology / Q000473:pathology; D038223:Post-Concussion Syndrome / Q000201:enzymology / Q000473:pathology
D020169:Caspases