THE EFFECT OF MANNITOL ON EXPERIMENTAL CEREBRAL-ISCHEMIA, REVISITED

THE EFFECT OF 20% mannitol on ischemic neuronal injury was examined in male Wistar rats (n = 80) that were randomly divided into forebrain a nd focal ischemia groups. The animals were further subdivided into con trol, treatment with mannitol before ischemia (1 g/kg of body weight, 12 min before ischemia), and treatment with mannitol after ischemia (0 .25 g/kg of body weight, beginning 20 min after ischemia and then ever y 6 h for 48 h) groups. Physiological parameters were carefully monito red and maintained within normal limits. The administration of mannito l after ischemia was found to produce a statistically significant impr ovement in ischemic neocortical injury and selective neuronal necrosis in the neocortex in the forebrain and focal models, respectively. How ever, treatment with mannitol after ischemia was shown not to favorabl y alter histopathological outcome in hippocampal levels 2 through 7 in the forebrain model nor did it reduce infarct volume in the focal isc hemia group. Treatment with mannitol before ischemia did not produce s tatistically significant reductions in neuronal injury in either model . These results do not support the findings of previous investigations , which have demonstrated that mannitol affords a significant degree o f neuroprotection when administered either before or immediately after vessel occlusion in models of forebrain and focal cerebral ischemia. The neuroprotective effect of mannitol demonstrated in the neocortex o f both forebrain and focally ischemic rats may support the theory that the main mechanisms responsible for neocortical injury in ischemia di ffer from those in the striatum hippocampus. Finally, mannitol's abili ty to reduce ischemic neuronal injury most effectively when administer ed after rather than before the production of ischemia is consistent w ith a possible beneficial influence on the development of delayed cere bral edema.