To evaluate the location and early time course for development of cerebral edema following therapy for diabetes, streptozotocin-diabetic rats were subjected to constant i.v. infusion with saline and regular insulin. At the end of 1, 2, and 5 h of therapy, these rats were killed and tested for density of the cerebral cortex, subcortical white matter, caudate-putamen, thalamus, and medulla. Density data from treated animals were compared with those from control animals. From these data, change in brain tissue volume as water was calculated.
Diabetic animals killed after 1 h of fluid and insulin therapy demonstrated a modest increase in brain water content of all areas tested except white matter. Following 2 h of therapy, all regions tested were edematous, with a magnitude of edema that was similar to that seen at 1 h. After 5 h of therapy, there was further increase in water content of the cerebral cortex, but not the other regions examined. Treatment with saline alone did not result in central overhydration.
The findings of this study suggest that aggressive therapy with fluids and insulin, but not fluid alone, results in global overhydration of the brains of diabetic animals. Prolonged fluid and insulin treatment with a return of blood glucose to normal values causes further and preferential accumulation of edema fluid in the cerebral cortex.
