Combined treatment with nicardipine, phenobarbital, and methylprednisolone ameliorates vasogenic brain edema

Free radicals formed around the edematous areas of the brain can cause lipoperoxidation of the cellular membrane, followed by calcium influx into the cell through calcium channels. These secondary insults may aggravate vasogenic brain edema. Since phenobarbital is a free radical scavenger, methylprednisolone has an antilipoperoxidation effect; and nicardipine is a calcium channel blocker, we hypothesized that combined treatment with phenobarbital, methylprednisolone, and nicardipine would be beneficial in vasogenic brain edema. This hypothesis was tested in Sprague-Dawley rats with a transdural cold-injury on the right parietal cortex. The animals were randomly divided into two groups. Animals in the treatment group were injected intraperitoneally with phenobarbital (4 mg/kg), methylprednisolone (50 mg/kg), and nicardipine (10 micrograms/kg) at 5 min and 8 hours after the cold-injury. The control animals were injected with saline. These animals were sacrificed 24 hours after the injury. The extent of brain edema was assessed by measuring the water content, the inulin distribution volume, and the distribution area of Evans blue in the brain. Our results showed that the water content of the edematous hemisphere was similar in the control and the treatment groups. However, Evans blue distribution area and inulin distribution volume of the treatment group were less than those of the control group by 12% and 31%, respectively. In conclusion, the combined treatment with phenobarbital, methylprednisolone and nicardipine is beneficial in vasogenic brain edema.