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It has been asserted that reduction of colloid oncotic pressure (COP) can aggravate traumatic brain edema. To explore this issue, the authors measured the effect of COP reduction, with and without a simultaneous decrease in osmolality, on the development of brain edema after fluid percussion injury (FPI).Isoflurane-anesthetized Wistar rats received a 2.7-atm right parasagittal FPI followed by isovolemic exchange with (1) normal saline (NS); (2) half-normal saline (0.5 NS); (3) whole blood (WB); or (4) hetastarch (Hespan, Dupont). Shed blood (16 ml) was replaced with donor erythrocytes suspended in the study fluid. The WB group received heparinized fresh donor WB. Central venous pressure was maintained with additional study fluid as required. The specific gravity (SG) of the cortex and subcortex near the impact site was determined 4.5 h after FPI. The water content of the hemispheres was also determined using the wet-dry method. To define the status of the blood-brain barrier in the non-FPI hemisphere, two additional groups (FPI, non-FPI) were studied. Both groups received 30 mg/kg Evans' blue and NS at 4 ml/kg1/h sup -1. Four hours after FPI, the concentration of Evans' blue in the hemispheres was determined.After exchange, COP (mmHg +/- SD) decreased in the NS (9.6 +/- 2.1) and 0.5 NS (8.5 +/- 0.5) groups and was unchanged in the WB (16.7 +/- 3.3) and hetastarch (18.9 +/- 1.1) groups. Osmolality was unchanged in the WB group (295 +/- 5 mOsm/kg), increased in the NS (304 +/- 3 mOsm/kg) and hetastarch (306 +/- 2 mOsm/kg) groups, and was decreased in the 0.5 NS group (261 +/- 6 mOsm/kg). The Evans' blue data indicated that FPI resulted in blood-brain barrier damage in both hemispheres. In all four exchange groups, the SG of both cortical and subcortical tissue was less (indicating greater water content) in the impact hemisphere than in the nonimpact hemisphere. The SG was less in both hemispheres, although it was less in both hemispheres in the NS and 0.5 NS groups than in the WB and hetastarch groups. The lowest SG values were observed in the 0.5 NS group. The wet-dry water content determinations yielded a similar pattern of edema formation.These data, while confirming the important edematogenic effect of decreased osmolality, indicate that COP reduction per se can also aggravate brain edema after a mild to moderate mechanical head injury.