Propofol has been shown to have neuroprotective properties. However, the effect of propofol administration time on neuroprotection is not well understood. This study was conducted to determine if propofol administration time would influence its neuroprotective effects on an in vitro ischemia-reperfusion model, with special attention directed toward NMDA-induced calcium influx.

Primary mixed cortical cultures of thirteen-day-old rats were exposed to 5 min of oxygen-glucose deprivation (OGD), followed by 2 hr of reperfusion. Propofol (1-100µM) was administered before OGD or administered from the time of OGD to the end of the reperfusion period. In the blank and full kill groups, no drug or NMDA 500µM treatment was given. The surviving cells were counted using trypan-blue staining, and cell death rate (CDR) was determined. To measure the maximum Ca²⁺ influx, 50µM propofol was pre-treated or co-treated with 100µM NMDA. In the control and NMDA 100µM groups, no drug or NMDA 100µM was given. A P < 0.05 was considered statistically significant.

Cells pre-treated with propofol (10-100µM) or co-treated (50-100µM) at the time of OGD injury had a decreased CDR compared to the blank group. Cells pre-treated (2,713 nA) or co-treated (3,626 nA) with propofol had a decreased maximum Ca²⁺ influx compared to the 100µM NMDA group (4,075 nA). Cells pre-treated with propofol had a decreased maximum Ca²⁺ influx compared to co-treated rats.

Propofol demonstrated neuroprotective effects at lower concentrations when administered prior to OGD injury. This may be partially attributable to the reduction of Ca²⁺ influx against NMDA receptor activation.