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Abstract Details

Determining the molecular drivers of neurodegeneration using a novel in vitro model of secondary brain injury
Neuro Trauma and Critical Care
P11 - Poster Session 11 (11:45 AM-12:45 PM)

Neuronal cell death and degeneration are most apparent hours to days post TBI suggesting crosstalk between neurons, glia, and endothelial cells. We lack specific TBI biomarkers for accurate diagnosis and possible targets for therapy. Understanding the intercellular communication driving secondary brain injury will enable identification of potential therapeutic targets and development of diagnostic biomarkers.

To determine cell specific molecular drivers of secondary neurodegeneration and cell death following a TBI using a novel in vitro model.

N2a cells (a mouse neuroblastoma cell line) will be differentiated into neuron-like cells using either retinoic acid (RA) for cortical type neurons or dibutyryl-cAMP (dcAMP) for dopaminergic neurons on Bioflex® silastic membrane plates. Cell Injury Controller II will be used to injure neuron-like cells grown on a silastic membrane by inducing a biaxial stretch injury from expelled inert gas resembling physical stress experienced by brain cells during a TBI. Using selective elimination and filtration the class of molecules present in conditioned media most responsible for promoting secondary brain injury will be determined by using metabolic approaches, immunohistochemistry, and cell viability assays.

Our preliminary data obtained using undifferentiated N2a cells plated on Bioflex® culture plates showed that “conditioned” media collected from injured cells caused neurodegeneration and cell death when transferred onto naïve N2a cells.

Factors released by mechanically injured N2a cells promote apoptosis in naïve N2a cells. Preliminary data from our in vitro model of secondary brain injury suggests that conditioned media from injured differentiated neuron-like cells may also affect the health of naïve neuron-like cells providing a more biorelevant platform to identify the factors most responsible for driving secondary brain injury using methods above.

Gabriel R. Arismendi, MD (Rutgers New Jersey Medical School)
Dr. Arismendi has nothing to disclose.
No disclosure on file
No disclosure on file
Bruce A. Citron, PhD (VA New Jersey Health Care System) The institution of Dr. Citron has received research support from Department of Veterans Affairs.
No disclosure on file