Mannitol is frequently used to reduce elevated intracranial pressure o
ften associated with brain edema. In cases of a damaged blood-brain ba
rrier, however, mannitol might aggravate vasogenic cerebral edema, as
has recently been stressed. The aim of this study was to investigate w
hether multiple doses of mannitol administered during development of v
asogenic brain edema following a cryogenic cortical injury affect hemi
spheric swelling and edema. Sprague-Dawley rats were anesthetized with
ketamine and xylazine. A cortical freezing lesion was applied to the
right parietal region. A first series of eight rats received four dose
s of 20% mannitol (0.4 g/kg within 10 minutes) thirty minutes, 3, 6 an
d 9 hours after trauma. Twelve hours after cryogenic injury, the brain
s were removed for determination of hemispheric swelling and cerebral
water content. Eight control rats were infused with saline only. In a
second series nine rats received eight doses of 20% mannitol 30 minute
s, 3, 6, 9, 12, 15, 18 and 21 hours after trauma. In this series, the
brains were removed 24 hours after freezing. Again respective control
animals were infused with saline only. Hemispheric swelling was 7.2 +/
- 0.5% after four doses of mannitol compared to 7.6 +/- 0,5% in contro
l animals (n.s.). Following eight doses of mannitol hemispheric swelli
ng was 8.9 +/- 0.4% compared to 10.1 +/- 0.4% in control rats (p < 0.0
5). Accordingly, the water content of traumatized hemispheres was lowe
r following repeated mannitol treatment (80.5 versus 80.8%). Water con
tent in control hemispheres was not affected by mannitol. Taken togeth
er, these results indicate that multiple doses of mannitol do not aggr
avate total hemispheric swelling, nor global water content following i
nduction of vasogenic edema. In contrast, repeated administration of m
annitol reduces traumatic swelling, thus favouring repeated mannitol a
pplication even when the blood-brain barrier is defective.