Ischemia in normo- and hyperglycemic rats: effects on brain water and electrolytes.

Abstract

Previous investigations have shown that preischemic hyperglycemia worsens cerebral outcome. This study sought to delineate the temporal relations between postischemlc brain edema and the development of spontaneous epileptic activity. Fasted rats were subjected to 10 minutes of forebrain ischemia. One-half of the animals were made hyperglycemic by glucose infusion prior to ischemia. At serial recirculation intervals regional specific gravity and cortical electrolytes were measured. Normoglycemic animals showed a biphasic increase in brain water content that was fully resolved by 96 hours and had no convulsive activities. Hyperglycemic brains, although displaying a slower resolution from an initial transient decrease in specific gravity, also developed an interval with normal water content that persisted at 18 hours postischemia. At 24 hours, an increase in water content recurred and was soon followed by the onset of seizure activity. Cortical electrolyte changes were unremarkable until seizures occurred. Significant increases in total Na + , Cl", and Ca 2+ and a decrease in K + were then seen. We conclude that while the normoglycemic brain is capable of resolving postischemic edema in this model, the hyperglycemic brain develops a delayed secondary increase in water content followed by the onset of seizure activity accompanied by a deterioration of ionic homeostasis. The pathophysiology of this ischemic edema has been intensely explored in animal experiments. 2 " 7 Such studies demonstrate that the early swelling, noticeable within the first 30 minutes of vascular occlusion, is due to cellular ("cytotoxic") edema; later, a vasogenic mechanism with extravasation of proteins contributes to fluid accumulation. 18It is less clear to what extent edema contributes to the brain damage incurred as a result of transient ischemia. Long periods of global or regional ischemia (30-60 minutes) are followed by accumulation of water, with electrolyte changes characteristic of cellular edema.*" 12 Under favorable conditions, though, the edema is transient. Controversy revolves around the question of whether a vasogenic component contributes to yield a secondary increase in tissue water content. Thus, while one group has reported that ischemia as brief as 5 minutes will cause vasogenic edema after a delay of many hours, 8 " another group has published results demonstrating that transient ischemia of 30 minutes duration does not cause vasogenic edema unless the ischemia gives rise to infarction. 10The question of whether edema contributes to the final damage resulting from transient ischemia received increased attention when it was shown that preischemic hyperglycemia aggravates damage, and that macro-and microscopic swelling was a conspicuous feature in this aggravation.13 " 16 The question also Received April 3, 1986; accepted November 21, 1986. arose whether the exaggerated extra-and intracellular acidosis in hyperglycemic animals caused edema. 17 In this study, we exploited the fact that while most fasted animals exposed to...

Hyperglycemia Exacerbates Brain Edema and Perihematomal Cell Death After Intracerebral Hemorrhage

“…35 Previous experimental studies have demonstrated that hyperglycemia worsens acute BBB injury after transient forebrain ischemia in rats and accentuates brain edema. 5,6,36,37 The summarized speculations for hyperglycemia-induced brain injury are as follows. (1) Free radical formation is increased with hyperglycemia-induced brain injury.…”

Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep.

“…- 48 Secondary tissue edema is also associated with necrosis, at least in adult animals. 15 - 49 We have shown in a previous study that distinct electrophysiological phases of depression, epileptiform activity, and subsequent loss of intensity are associated with laminar necrosis of the underlying cortex.…”

Hypoglycemia prevents increase in lactic acidosis during reperfusion after temporary cerebral ischemia in rats

“…49 Lack of increase in water content as a manifestation of edema in either group was also unexpected. 6 It is possible that the 3°C drop in brain temperature observed during ischemia in pilot studies with this model could have a protective effect on edema, lipolysis, and excitotoxin release that masked any additional benefit of insulin treatment. Although previous MRS studies after 60 min of temporary global ischemia in normoglycemic rats did demonstrate elevated arachidonate and glutamate levels after 2 h of reperfusion, 28 we have no data after 5 h reperfusion or at earlier time points after 30 min of temporary ischemia.…”

“…Hyperglycemia has been shown to increase ischemic lactic acidosis 1 and cellular damage experimentally [2][3][4][5][6] and clinically, 7 whereas hypoglycemic animals have less acidosis than those studied under normoglycemic and hyperglycemic conditions. [8][9][10] However, potentially protective effects of insulin-induced hypoglycemia on energy metabolism and outcome are not consistently observed.…”