The effects of post-traumatic administration of glucose 2.0 g/kg was compared to saline infusion with and without control of brain temperature at 37 degrees C on behavioral and histological measures of brain injury after controlled cortical impact injury complicated by a secondary ischemic insult. The glucose infusion increased blood glucose concentration from 114 +/- 4 to 341 +/- 76 mg/dl prior to the secondary ischemic insult. The resulting outcome measures were significantly worse in the glucose infusion group than in either control group. Mortality rate was significantly increased by the glucose administration, from 0% to 55% (p < 0.001). The median contusion volume was increased from 7.9 to 64.2 by glucose administration (p < 0.001) and the neuronal loss in the CA1 and CA3 areas of the hippocampus were greater in the glucose infusion group. In the animals that survived for the 2 weeks of behavioral studies, the duration of beam balance was shorter; the percent of animals that could balance on the beam for at least 60 s was less, the percent of animals that could perform the beam-walking task was less, and the length of time required to find the platform in the Morris water maze task was longer in the glucose infusion group. These studies demonstrate that the infusion of glucose after the cortical impact injury significantly increases the damage caused by post-traumatic ischemic insults. The adverse effect on neurological outcome could not be explained by the temperature effects of glucose infusion.