INTRACEREBRAL INFUSION OF THROMBIN AS A CAUSE OF BRAIN EDEMA

Purified thrombin from an exogenous source is a hemostatic agent commo nly used in neurosurgical procedures. The toxicity of thrombin in the brain, however, has not been examined. This study was performed to ass ess the effect of thrombin on brain parenchyma, using the formation of brain edema as an indicator of injury. Ten mu l of test solution was infused stereotactically into the right basal ganglia of rats. The ani mals were sacrificed 24 hours later, and the extent of brain edema and ion content were measured. Concentrations of human thrombin as low as 1 U/mu l resulted in a significant increase in brain water content. R ats receiving 10 U/mu l had a mortality rate of 33% compared to no mor tality in the groups receiving smaller doses. Thrombin-induced brain e dema was inhibited by a specific and potent thrombin inhibitor, hirudi n. A medical grade of bovine thrombin commonly used in surgery also ca used brain edema when injected at a concentration of 2 U/mu l. Edema f ormation was prevented by another highly specific thrombin inhibitor, N halenesulfonylglycyl)-4-DL-phenylalaninepiperidide (alpha-NAPAP). Th rombin-induced brain edema was accompanied by increases in brain sodiu m and chloride contents and a decrease in brain potassium content. Cha nges in brain ions were inhibited by both hirudin and alpha-NAPAP, cor responding to the inhibition of brain water accumulation. This study s hows that thrombin causes brain edema when infused into the brain at c oncentrations as low as 1 U/mu l, an amount within the range of concen trations used for topical hemostasis in neurosurgery.