Accumulated mannitol and aggravated cerebral edema in a rat model of middle cerebral artery infarction.

OBJECTIVE

Repeated administration of mannitol in the setting of large hemispheric infarction is a controversial and poorly defined therapeutic intervention. This study was performed to examine the effects of multiple-dose mannitol on a brain edema after large hemispheric infarction.

METHODS

A middle cerebral artery was occluded with the rat suture model for 6 hours and reperfused in 22 rats. The rats were randomly assigned to either control (n=10) or the mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg) were performed six times every four hours. After staining a brain slice with 2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH) and contralateral (CH), and the IH/CH weight ratio were examined, and then hemispheric accumulation of mannitol was photometrically evaluated based on formation of NADH catalyzed by mannitol dehydrogenase.

RESULTS

Mannitol administration produced changes in body weight of -7.6+/-1.1%, increased plasma osmolality to 312+/-8 mOsm/L. It remarkably increased weight of IH (0.77+/-0.06 gm versus 0.68+/-0.03 gm : p<0.01) and the IH/CH weight ratio (1.23+/-0.07 versus 1.12+/-0.05 : p<0.01). The photometric absorption at 340 nm of the cerebral tissue in the mannitol-treated group was increased to 0.375+/-0.071 and 0.239+/-0.051 in the IH and CH, respectively from 0.167+/-0.082 and 0.162+/-0.091 in the IH and CH of the control group (p<0.01).

CONCLUSIONS

Multiple-dose mannitol is likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in the infarcted brain tissue.