? ? Oligodendrocyte (oligo) cell death occurs in response to several pathophysiological processes, including ischemia, hypoxia, infection and trauma. Several laboratories have shown that oligos in the above models of injury die or are damaged by excessive amounts of the neurotransmitter glutamate. However, there are varying reports of just how susceptible oligos are to glutamate, and it is not known what factors are responsible these differing results. The proposed studies will begin to determine how the extracellular environment in a damaged central nervous system (CNS) changes oligos' response to glutamate. This proposal will focus on how two factors - oxygen changes and the presence of microglia - affect oligos vulnerability to toxic substances released during CNS trauma and disease. Using Oligodendrocyte and microglia cultures, both in isolation and combination, along with oxygen-regulating incubators and the glutamate receptor agonist kainic acid, the proposed experiments will help determine what conditions and cellular responses in the CNS mediate oligo death, and provide insights into future therapies to protect oligos in multiple diseases. ? ? ?
|Ferguson, Adam R; Christensen, Randolph N; Gensel, John C et al. (2008) Cell death after spinal cord injury is exacerbated by rapid TNF alpha-induced trafficking of GluR2-lacking AMPARs to the plasma membrane. J Neurosci 28:11391-400|
|Miller, Brandon A; Crum, Jeannine M; Tovar, C Amy et al. (2007) Developmental stage of oligodendrocytes determines their response to activated microglia in vitro. J Neuroinflammation 4:28|