Although neuroprotection to contain the initial damage of spinal cord injury (SCI) is difficult, multicentre studies show that early neurosurgery under general anaesthesia confers positive benefits. An interesting hypothesis is that the general anaesthetic itself might largely contribute to neuroprotection, although in vivo clinical settings hamper studying this possibility directly. To further test neuroprotective effects of a widely used general anaesthetic, we studied if propofol could change the outcome of a rat isolated spinal cord SCI model involving excitotoxicity evoked by 1 h application of kainate with delayed consequences on neurons and locomotor network activity. Propofol (5 μm; 4-8 h) enhanced responses to GABA and depressed those to NMDA together with decrease in polysynaptic reflexes that partly recovered after 1 day washout. Fictive locomotion induced by dorsal root stimuli or NMDA and serotonin was weaker the day after propofol application. Kainate elicited a significant loss of spinal neurons, especially motoneurons, whose number was halved. When propofol was applied for 4-8 h after kainate washout, strong neuroprotection was observed in all spinal areas, including attenuation of motoneuron loss. Although propofol had minimal impact on recovery of electrophysiological characteristics 24 h later, it did not further depress network activity. A significant improvement in disinhibited burst periodicity suggested potential to ameliorate neuronal excitability in analogy to histological data. Functional recovery of locomotor networks perhaps required longer time due to the combined action of excitotoxicity and anaesthetic depression at 24 h. These results suggest propofol could confer good neuroprotection to spinal circuits during experimental SCI.