Differential Neuroprotective Effects of Interleukin-1 Receptor Antagonist on Spinal Cord Neurons after Excitotoxic Injury.

Secondary damage following spinal cord injury (SCI) induces neuronal damage through inflammatory and excitotoxic pathways. We hypothesized that the interleukin-1 receptor antagonist (IL1RA) protects neuronal populations and suppresses apoptosis and gliosis after injury. Spinal cord slice cultures (SCSCs) were subjected to excitotoxic injury with N-methyl-D-aspartate (NMDA) and treated with IL1RA. Immunohistochemistry for neuronal nuclei (NeuN), MacII, glial fibrillary acidic protein, and TdT-mediated dUTP nick end labelling stains were used to evaluate neuronal survival, glial activation, and apoptosis. Treatment with IL1RA significantly reduced the number of apoptotic cells in both NMDA-lesioned and unlesioned cultures. Experimental injury with NMDA reduced the number of NeuN-positive ventral horn neurons, and IL1RA treatment counteracted this loss 1 day after injury. However, IL1RA had no effect on the number of presumable Renshaw cells, identified by their selective expression of the cholinergic nicotinic α2-receptor subunit (Chrna2). Activated microglial cells were more numerous in NMDA-lesioned cultures 1 day after injury, and IL1RA significantly reduced their numbers. We conclude that IL1RA modulates neuronal apoptosis and microglial activation in excitotoxically injured SCSCs. Renshaw cells were more susceptible to excitotoxic injury than other neurons and were not rescued by IL1RA treatment. Modulation of IL-1-mediated pathways may thus be effective in reducing excitotoxically induced neuronal damage after SCI, however only in specific neuronal populations, such as ventral horn neurons. These findings motivate further investigations of the possibility to antagonize inflammatory pathways after SCI.