Comparison of the effects of hypertonic glycerol and urea on brain edema, energy metabolism and blood flow following cerebral microembolism in the rat. Deleterious effect of glycerol treatment.

Abstract

SUMMARY Cerebral microembolism was performed in rats by injecting radioactive calibrated 50 /x microspheres into the left internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 24 h after embolization by measuring brain water, sodium, and potassium content. Equiosmolal doses (40 mmol/kg) of glycerol or urea were injected i.p. at various times before sacrifice. Both treatments caused similar changes in water and electrolyte content, brain dehydration being maximal 30 min after urea and 2 h after glycerol injection. Cerebral energy metabolism and regional blood flow were evaluated at the times of maximal brain dehydration. Urea treatment resulted in an improvement of the cerebral circulation whereas glycerol treatment led to a deterioration of cerebral blood flow which cannot be explained by failure to reduce edema and the consequent microcirculatory impairment. Urea treatment had no marked effect on cerebral energy metabolism whereas glycerol injection resulted in an important increase in brain lactate level which may be relevant to the impairment of cerebral reperfusion. These results point out that administration of a metabolized solute like glycerol may exert deleterious effects on the ischemic brain.Stroke Vol 14, No 4, 1983 BRAIN EDEMA, a serious complication of cerebral infarction, is known to increase intracranial pressure and to alter cerebral hemodynamics and metabolism. Hyperosmolar solutions have been used extensively to reduce cerebral edema.' The mechanism of action of the hypertonic agents which do not readily cross the blood-brain barrier (BBB) is assumed to be related to intravascular hypertonicity leading to the extraction of tissue water by the osmotic gradient they create across the BBB. Among the hyperosmolar agents, glycerol attracted more attention than the other substances because in addition to its osmotic activity it can be metabolized by brain.2 " 4 Numerous experimental works [5][6][7][8][9][10][11][12][13] have reported the effect of glycerol or urea on brain water and electrolytes or on intracranial pressure but little is known about their actions on cerebral circulation and metabolism of the ischemic brain. The aim of the present study was to assess the effect of glycerol on brain edema, cerebral blood flow and metabolism compared to an equivalent dose of the metabolically inert urea. The study was performed on an experimental model of cerebral microembolism in the rat. I4 The cerebral injury in this model reproducibly results in important brain edema within 24 h of embolization. Brain water and electrolytes were determined at various times after injection of glycerol or urea. Regional cerebral blood flow and brain energy metabolism were evaluted at the times of maximal brain dehydration.Methods The experiments were performed on male SpragueDawley rats (Iffa Credo) weighing 280-320 g. Production and Evaluation of EmbolizationCerebral microembolism was produc...

Lipid metabolism, cerebral metabolic rate, and some related enzyme activities after brain infarction in rats.

“…' 31 Twenty-four hours after microsphere injection, the time of the present study, regional cerebral blood flow in the embolized hemisphere reached 30-50% of the control value, depending on the cerebral structure.…”

Circulating and Brain BDNF Levels in Stroke Rats. Relevance to Clinical Studies

“…In the present study, embolic stroke was induced by the injection into the left carotid circulation of 50 µm-calibrated microspheres, a model that results in severe ischemia of the left hemisphere and formation of multiple infarcts that primarily affects the parieto-temporal cortex, the hippocampus and the thalamostriate areas [21], [22]. This model is unique because it allows inducing a large but controlled distribution of degrees of stroke severity by changing the number of injected microspheres.…”

“…Nevertheless, even if reperfusion may be associated to the passage of BDNF from the brain into the blood, the detection in the blood of BDNF originating from the brain appears challenging because of a dilution effect of BDNF levels in the blood. Notably, a passage of BDNF from the brain to the blood is possible after embolization despite the lack of reperfusion as embolization is associated with both a disruption of the blood-brain barrier and a residual blood flow [20], [22].…”

“…Indeed, we previously reported a strong correlation between the degree of cerebral embolization and clinically-pertinent markers of stroke severity including brain depletion in the neuronal marker N-acetyl-aspartate, vasogenic edema and acute neurological deficit [20]–[22]. In order to quantify the degree of cerebral embolization, the centrifugation pellets of brain tissue were dissolved in 5 ml of 20% KOH and centrifuged (500 g).…”

Time course of changes in brain energy metabolism of the rat after microsphere-induced cerebral embolism.

“…Therefore, more sophisticated ischemic models are required for assessment of pathophysiology of cerebral ischemia. Recently, microsphere-induced cerebral embolism has been shown to experimentally induce focal or regional ischemia in the brain of rats, cats and rabbits (11)(12)(13)(14)(15)(16)(17)(18). Using this type of model, the above investigators have mainly dealt with histological and behavioral changes of the animals after the brain ischemia.…”