Purified
thrombin from an exogenous source is a
hemostatic agent commonly used in
neurosurgical procedures. The toxicity of
thrombin in the brain, however, has not been examined. This study was performed to assess the effect of
thrombin on brain parenchyma, using the formation of
brain edema as an
indicator of injury. Ten microliters of test
solution was infused stereotactically into the right basal ganglia of rats. The animals 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/microliter resulted in a significant increase in brain water content. Rats receiving 10 U/microliters had a mortality rate of 33% compared to no mortality in the groups receiving smaller doses.
Thrombin-induced
brain edema was inhibited by a specific and potent
thrombin inhibitor,
hirudin. A medical grade of bovine
thrombin commonly used in surgery also caused
brain edema when injected at a concentration of 2 U/microliters.
Edema formation was prevented by another highly specific
thrombin inhibitor, N alpha-(2-Naphthalenesulfonylglycyl)-4-DL-phenylalaninepiperidid e (
alpha-NAPAP).
Thrombin-induced
brain edema was accompanied by increases in brain
sodium and
chloride contents and a decrease in brain
potassium content. Changes in brain
ions were inhibited by both
hirudin and
alpha-NAPAP, corresponding to the inhibition of brain water accumulation. This study shows that
thrombin causes
brain edema when infused into the brain at concentrations as low as 1 U/microliter, an amount within the range of concentrations used for topical hemostasis in neurosurgery.