Effects of Mannitol on Ischemia-Induced Degeneration in Rat Hippocampus

Abstract

Abstract. Although mannitol has been used as an osmotherapeutic drug on brain injury, the clinical efficiency of the drug are still controversial. In the present study, we examined the effects of mannitol on the edema in a hippocampal slice due to brief ischemia. To evaluate the effects, we employed an image analysis system that consists of an infrared-differential interference contrast (IR-DIC) microscope, an infrared CCD camera, and a computer with custom-made software. By this system, severity of the edema can be quantified as the coefficient of variation (CV) of digitalized slice images. The dose-dependent improvement on the deteriorated hippocampal slices could be obtained by administration of mannitol (10, 50, and 100 mM) after 10-min ischemia. However, field excitatory postsynaptic potentials (fEPSP) in CA1 stratum radiatum, which disappeared during 10-min ischemia, were never recovered by mannitol after more than 20-min treatment. fEPSP were blocked by the effective dose of mannitol for morphological recovery, but the effects found to be reversible. Although we failed to find positive rescuing effects of mannitol on the synaptic activities after ischemia, the protective effects of the drug on ischemic edema may rescue the secondary damages around the infarct area.

Evaluation of the Protective Effects of Cyclosporin A and FK506 on Abnormal Cytosolic and Mitochondrial Ca2+ Dynamics During Ischemia and Exposure to High Glutamate Concentration in Mouse Brain Slice Preparations

“…7). The fluorescence intensity tended to increase even after ACSF reperfusion, which had been demonstrated previously by using a specific method (43,44). CsA and FK506 showed no significant protective effects on the morphological dynamics in cells and mitochondria.…”

Effects of Combination Treatment with Dexamethasone and Mannitol on Neuronal Damage and Survival in Experimental Heat Stroke

“…32) Although mannitol cannot cross the blood brain barrier, it has a potent anti-edema action by drawing water from intracellular spaces into the intravascular space. 33) As a result, the brain has been thought to be rescued by lowering intracellular pressure, and thus by lowering intracranial pressure. Moreover, one of the nonosmotic mannitol effect is the protection against free radical-mediated ischemic cell damage.…”

“…6,9,11,14,15) Various clinical and experimental investigations have shown that single doses of dexamethasone (DXM; exogenous glucocorticoids) or mannitol are extensively used in the treatment of cerebral ischemia and/or cerebral injury. [16][17][18] In the studies of heat stroke, pretreatment with DXM attenuated serum IL-1b levels and improved survival in heat stroke. 19) Additionally, pretreatment with mannitol before the onset of heat stroke caused significant reduction of the heat strokeinduced the increased free radical formation and intracranial hypertension.…”