Enhancement of infusion-induced brain edema by mediator compounds.

Mediator compounds such as bradykinin, arachidonic acid, and LT are released in the brain in conditions causing cerebral swelling. The potential of these compounds to enhance this process was studied in the infusion-induced model of brain edema. Cats subjected to chloralose anesthesia were infused with 400 microliters of artificial CSF into the right and left frontal white matter within 2.5 hr. CSF infused into the left hemisphere contained either bradykinin (40 microM), arachidonic acid (3 mM), LTB4 (15 microM), or LTC4 (16 microM), respectively. Evans blue was administered as blood-brain barrier indicator. Water content of gray and white matter was microgravimetrically determined in serial coronal brain slices. Infusion of CSF only led to an increase in water content from 69 to between 75% and 79%. Addition of bradykinin effectively enhanced the infusion edema but did not open the barrier to Evans blue. Arachidonic acid even more effectively led to an increase in water content and opened the barrier to Evans blue, in addition. Infusion of LT (LTB4, as well as LTC4) was not found to increase further the infusion edema and did not open the blood-brain barrier to Evans blue. It is concluded that the infusion edema model is suitable for studying the edema-enhancing potential of mediator compounds. Marked enhancement of vasogenic brain edema by bradykinin or arachidonic acid again demonstrates a pathophysiological function of these compounds as mediators of secondary brain damage, although LT are unlikely to be specifically involved in vasogenic edema formation.