Modulation of Transcription Factor Nrf2 in an In Vitro Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) afflicts approximately 1.4 million people in the United States and TBIs have been labeled a major cause of death and disability on a global scale. Regulatory responses in a variety of neuronal loss conditions have supported the protective involvement of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor. Nrf2 regulates antioxidant enzyme genes, and an increase in Nrf2 expression may counteract oxidative damage that results from TBI. Elevated Nrf2 may ultimately act through the upregulation of downstream target genes such as thioredoxin (Trx) and heat-shock protein-70 (HSP70) and this may reduce neuronal loss. We performed multiple mild biaxial stretch injuries to neuroblastoma cells in culture, and examined the effects of the Nrf2 activator, tert-butylhydroquinone (tBHQ). We also compared the stretch injury to oxidative insult. We confirmed that Trx and HSP70 were upregulated by treatment with tBHQ. We observed that tBHQ protected neurons from either insult, and that this was evident by different measures of cell viability and a decrease in annexin V binding. Neuronal health after insult was improved approximately 50% by tBHQ, indicating that neurons exposed to TBI in vitro can be protected.

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Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

“…In fact, stretch inputs are among the most widely used in vitro models for the initial mechanical injury in TBI [42], and simple stretch injury culture systems have already offered insights into TBI disease pathology and drug screening [43,44,45]. Victims of TBI unfortunately often suffer from cognitive, behavioral, and memory problems, functions that are at least partially modulated by hippocampal NSCs [46].…”