The Influence of Propofol Administration Time on Oxygen Glucose Deprivation-Reperfusion Injury in Rat mixed Cortical Cultures Focused on N-Methyl-D-Aspartate (NMDA) Receptor

OBJECT: Excessive extracellular glutamate accmulation due to cerebral ischemia and reperfusion is belived to induce excitotoxic cascade mainly by overstimulation of N-methyl-D-aspartate (NMDA) receptors. Propofol have been known to have neuroprotective effects. However, the effect of administration time is not well known with in vitro model. This study was conducted to determine whether the propofol administration time would influence the neuroprotective effect on in vitro ischemia reperfusion model mainly focused on NMDA-induced neuronal damage by calcium influx. METHODS: Sprague-Dawley rats (250-300 gm) were used. Thirteen day old primary mixed cortical cultures were exposed to a 5 min combined oxygen glucose deprivation(OGD, in vitro ischemia model), followed by 2 hr reoxygenation(reperfusion). Propofol (1, 10 25, 50, 100 μM) were treated from 1 hr prior to the OGD injury (pre-treatment)or from the initiation of the OGD injury(co-treatment) to the end of the reperfusion periods. In Control group, no drug was treated and incubated in the aerobic chamber. In Blank and Full-kill group, no drug was treated during OGD-reperfusion injury. The survived cells were counted using trypan blue staining. The data were converted to cell death rate(CDR). To measure the effects of propofol administration time on the extent of Ca++ influx by NMDA receptor stimulation, 50 μM propofol were 1 hr pre-treated before 100 μM NMDA stimulation or co treated with 100 μM NMDA. In Control group, no drug was treated during the experiment. Statistical analysis were done by one-way ANOVA test and Bonferroni test. P<0.05 were considered as statistically significant. RESULTS: OGD-reperfusion demonstrated about 70 % cell death rate. Pre-treated 10-100 μM of propofol decreased the cell death rate compared with no drug treated group (P < 0.05). Co-treated 50-100 μM of propofol decreased the cell death rate compared to no drug treated group (P < 0.05). 50 μM of pre-treated (2908.63 nA) or co-treated (3544.10 nA) propofol decreased the extent of Ca++ influx compared with 100 μM NMDA alone treated group (4080.12 nA)(P < 0.05). 50 μM of pre-treated propofol decreased the extent of Ca++ influx compared with co-treated propofol against 100 μM NMDA stimulation (2908.63 vs 3544.10 nA) (P < 0.05). CONCLUSION: Pre-administered propofol demonstrated neuropreotective effect at more lower concentration compared with co-treated propofol (10 μM vs 50 μM) which could partly by the reduction of Ca++ influx against NMDA receptor activation.

Author dc:creator

• 김, 은진

Contributors dc:contributor

• 이, 숙영
• 대학원 의학과
• 200624540

• propofol
• NMDA receptor
• oxygen glucose deprivation-reperfusion Injury

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000009282
000000009282

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1823