The ability of GRP78 targeting specific astroglia to protect from traumatic brain injury in vitro.

Brain injury is a major public health problem, especially among male adolescents and young adults ages 15 to 24, and among elderly people of both sexes 75 years and older. Despite the major improvements in the acute care of head injury victims, no effective pharmaceutical strategies exist for preventing the secondary injury cascade, oxidative stress and metabolic dysfunctions that occur afterwards. In the present study, we will study the role of astrocyte mitochondrial impairment in brain injury by targeting expression of GRP78 selectively to astrocytes, as this is our neuroprotective strategy. This can be accomplished by using a GRP78 overexpressing stable C6 cell line. This will let us test the importance of protecting astrocyte mitochondria in the setting of traumatic brain injury in vitro. Therefore, in this study, we will examine the effects of GRP78 on astrocyte cell death, morphology and activation, oxidative stress, and migration using an in vitro model to follow the astrocytic response of a scratch wound inflicted on a monolayer of cultured C6 astroglioma.