Neuroprotective effect of propofol against excitotoxic injury to locomotor networks of the rat spinal cord invitro

被引:21
作者
Kaur, Jaspreet [1 ]
Gutierrez, Javier Flores [1 ]
Nistri, Andrea [1 ,2 ]
机构
[1] Int Sch Adv Studies SISSA, Neurosci Dept, Via Bonomea 265, I-34136 Trieste, Italy
[2] Ist Med Fis & Riabilitaz, SPINAL, Udine, Italy
关键词
general anaesthetic; kainic acid; motoneuron; spinal cord injury; ACID-INDUCED RESPONSES; NEURONAL DAMAGE; ANTIOXIDANT CAPACITY; GABA(A) RECEPTORS; ANESTHETIC AGENT; INHIBITOR PJ-34; SLICE CULTURES; INFARCT SIZE; VENTRAL HORN; BRAIN-STEM;
D O I
10.1111/ejn.13353
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 invivo 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 1h application of kainate with delayed consequences on neurons and locomotor network activity. Propofol (5m; 4-8h) enhanced responses to GABA and depressed those to NMDA together with decrease in polysynaptic reflexes that partly recovered after 1day 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 4-8h 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 24h 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 24h. These results suggest propofol could confer good neuroprotection to spinal circuits during experimental SCI.
引用
收藏
页码:2418 / 2430
页数:13
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