Modeling the pathobiology of repetitive traumatic brain injury in immortalized neuronal cell lines

• Published in: Brain research 2011-11, Vol.1425, p.123-131
• Main Authors: Kane, Michael J, Hatic, Haris, Delic, Vedad, Dennis, John S, Butler, Carrie L, Saykally, Jessica N, Citron, Bruce A
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; anxiety; Biological and medical sciences; brain; Brain Injuries - enzymology; Brain Injuries - pathology; caspases; Caspases - metabolism; Cell Count - methods; Cell Differentiation - physiology; Cell Line, Transformed; Cell Line, Tumor; Cell survival; Cell Survival - physiology; cognition; genetic engineering; HT22 hippocampal cell; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; memory; Neurite; neurites; Neurites - enzymology; Neurites - pathology; Neurology; Organic mental disorders. Neuropsychology; pathophysiology; patients; Post-Concussion Syndrome - enzymology; Post-Concussion Syndrome - pathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; public health; SH-SY5Y neuroblastoma cell; Traumas. Diseases due to physical agents; Traumatic brain injury; viability
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2011.09.047

Abstract 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.