The early stages of spinal cord injury (SCI) start with excitotoxic damage caused by a massive release of glutamate. However, glutamate release is not the only factor to consider. Inflammatory molecules like tumor necrosis factor alpha (TNFα), belonging to a group of cytokines initially identified and named for their ability to kill tumor cells, is also a key factor in neuronal death and inflammation. TNFα is released from macrophages and activated microglia following a SCI, reaching a peak 1 h after the primary injury. Motoneurons whose survival is necessary for successful rehabilitation are especially vulnerable to the effects of TNFα release. While TNFα has been postulated to increase glutamatergic synaptic transmission, evidence for this has been indirect. Here, we show using whole-cell recording from lumbar motoneurons that AMPA and NMDA receptor-mediated excitatory postsynaptic currents are rapidly increased following bath application of TNFα. Concurrently, the single-channel open probability of AMPA and NMDA channels were also augmented by TNFα. Overall, our data lead us to propose the idea that motoneuronal vulnerability to excitotoxicity is not only due to the excessive release of glutamate, but may also be attributable to the increased sensitivity of AMPARs and NMDARs to the proinflammatory factor, TNFα, released after SCI.
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