| 1. |
- Harris, R. J., et al.
(author)
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Cerebral extracellular calcium activity in severe hypoglycemia : Relation to extracellular potassium and energy state
- 1984
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 4:2, s. 187-193
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Journal article (peer-reviewed)abstract
- The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at ∼13 mM, was associated with a fall in Cae. Ke peaked at 48 ± 12 mM, and Cae at 0.18 ± 0.28 mM. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity, but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at ∼13 mM, was associated with a fall in Cae. Ke peaked at 48 ± 12 mM, and Cae at 0.18 ± 0.28 mM. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity, but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.The changes in extracellular Ca2+ (Cae) and K+ (Ke) activities were studied in the rat brain during insulin-induced hypoglycemia. At about the time of onset of isoelectric EEG in severe insulin-induced hypoglycemia (300-g male Wistar rats under 70% N2O anaesthesia), there was an increase in Ke which, at ∼13 mM, was associated with a fall in Cae. Ke peaked at 48 ± 12 mM, and Cae at 0.18 ± 0.28 mM. This ion change began to normalise, but before recovery was complete a second ion change, of magnitude similar to that of the first, occurred from which the cells did not recover. The Cae recovered to only 66% of normal in the time available before the second depolarisation. Measurements on brains frozen at different stages during the sequence of ion changes revealed that ATP and phosphocreatine (PCr) concentrations and energy charge (EC) were not reduced before the first depolarisation. During the first depolarisation there was a 72% decrease in PCr and a 37% fall in ATP level, leading to a 23% drop in EC. These levels decreased further by the 10th minute of isoelectricity, but only the fall in ATP concentration was significant. The results indicate that the first ion change was a spreading depression and that cellular energy state was not the only factor in determining the response of tissue in the early stages of the comatose state.
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| 3. |
- Wieloch, Tadeusz, et al.
(author)
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Influence of Severe Hypoglycemia on Brain Extracellular Calcium and Potassium Activities, Energy, and Phospholipid Metabolism
- 1984
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 43:1, s. 160-168
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Journal article (peer-reviewed)abstract
- Abstract: In the cerebral cortices of rats, during insulininduced hypoglycemia, changes in the concentrations of labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)] and glycolytic metabolites (lactate, pyruvate, and glucose) as well as phospholipids and free fatty acids (FFAs) were studied in relation to extracellular potassium and calcium activities. Changes in extracellular calcium and potassium activities occurred at approximately the onset of isoelectricity. The extracellular calcium activity dropped from 1.17 ± 0.14 mM to 0.18 ± 0.28 mM and the potassium activity rose from 3.4 ± 0.94 mM to 48 ± 12 mM (means ± SD). Minutes prior to this ionic change the levels of ATP, PCr, and phospholipids were unchanged while the levels of FFAs remained unchanged or slightly elevated. Following the first ionic change the steady‐state levels of ATP decreased by 40%, from 2.42 to 1.56 μmol/g. PCr levels decreased by 75%, from 4.58 to 1.26 μmol/g. Simultaneously, the levels of FFAs increased from 338 to 642 nmol/g, arachidonic acid displaying the largest relative increase, 33 to 130 nmol/g. The first ionic change was followed by a short period of normalization of ionic concentrations followed by a sustained ionic change. This was accompanied by a small additional decrease in ATP (to 1.26 μmol/g). The FEA levels increased to 704 nmol/g. There was a highly sig nificant negative correlation between the levels of FFAs and the energy charge of the tissue. The formation of FFAs was accompanied by a decrease in the phospholipid pool. The largest relative decrease was observed in the inositol phosphoglycerides, followed by serine and ethanolamine phosphoglycerides. After 10 min of isoelectricity the levels of phospholipids had decreased by 5.12 μmol/g while the levels of FFAs had increased by 0.46 μmol/g, indicating oxidative metabolism or washout of the released FFAs. The attenuation of the rapid initial changes in the levels of the energy metabolites and FFAs as well as the correlation between the energy charge and the levels of FFAs suggests that a new steady state is established following the first ionic change. The importance of these reactions for the development of hypogiycemic neuronal damage is discussed.
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