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