Regional Localization of Cerebral Edema Following Fluid and Insulin Therapy in Streptozotocin-Diabetic Rats

Abstract

To evaluate the location and early time course for development of cerebra 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.

The UK case–control study of cerebral oedema complicating diabetic ketoacidosis in children

“…High doses of insulin may also be a risk factor for cerebral oedema, as indicated by animal models [26,27] and supported by our observational studies. Finally, the dangers inherent in using large volumes of relatively dilute fluids have been highlighted by many studies [5,7,17].…”

Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin

“…42,43 Arief and Kleeman 44,45 have reported that insulin enhances the transport of electrolytes into the central nervous system, which may cause addition of osmotically active particles to brain tissue that could cause an uptake of osmotic water. In humans, John et al 46 suggested that the insulin-driven Na ϩ /H ϩ antiport might increase intracellular fluid by promoting Na ϩ influx into brain cells.…”

Do doctors cause or prevent cerebral edema in children with diabetic ketoacidosis?

“…Tornheim (17) extended the examination of the role of insulin in the induction of cerebral edema by treating streptozotocin‐induced diabetes in rats with varying intravenous fluid and insulin doses. Brain tissue density was not significantly altered by infusion of half normal saline over 5 h, but when insulin was added to the same fluid regimen, edema was significantly increased in all parts of the brain, particularly in the grey matter.…”