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- Agardh, Carl-David, et al.
(författare)
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Hypoglycemic brain injury: metabolic and structural findings in rat cerebellar cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration
- 1981
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 1:1, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- Previous results have shown that severe, prolonged hypoglycemia leads to neuronal cell damage in, among other structures, the cerebral cortex and the hippocampus but not the cerebellum. In order to study whether or not this sparing of cerebellar cells is due to preservation of cerebellar energy stores, hypoglycemia of sufficient severity to abolish spontaneous EEG activity was induced for 30 and 60 min. At the end of these periods of hypoglycemia, as well as after a 30 min recovery period, cerebellar tissue was sampled for biochemical analyses or for histopathological analyses or for histopathological analyses by means of light and electron microscopy. After 30 min of hypoglycemia. the cerebellar energy state, defined in terms of the phosphocreatine, ATP, ADP, and AMP concentrations, was better preserved than in the cerebral cortex. After 60 min, gross deterioration of cerebellar energy state was observed in the majority of animals, and analyses of carbohydrate metabolites and amino acids demonstrated extensive consumption of endogenous substrates. In spite of this metabolic disturbance, histopathologic alterations were surprisingly discrete. After 30 min, no clear structural changes were observed. After 60 min, only small neurons in the molecular layer (basket cells) were affected, while Purkinje cells and granule cells showed few signs of damage. The results support our previous conclusion that the pathogenesis of cell damage in hypoglycemia is different from that in hypoxia-ischemia and indicate that other mechanisms than energy failure must contribute to neuronal cell damage in the brain.
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| 2. |
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| 3. |
- Agardh, Carl-David, et al.
(författare)
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Neurophysiological recovery after hypoglycemic coma in the rat: correlation with cerebral metabolism
- 1983
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 3:1, s. 78-85
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Tidskriftsartikel (refereegranskat)abstract
- Recovery of electroencephalographic activity and somatosensory evoked responses was studied in paralyzed and lightly anesthetized (70% N2O) rats in which profound hypoglycemia had been induced by insulin administration. The duration of severe hypoglycemia was defined as the duration of a flat electroencephalogram (EEG) recording (5, 30, and 60 min, respectively) before restitution with glucose. The restitution period was followed by continuous EEG monitoring and repeated tests for evoked potentials. After 180 min of recovery, the brains were frozen in situ with liquid nitrogen and analyzed for energy metabolism. In accordance with earlier metabolic studies from this laboratory, the recovery after 60 min of severe hypoglycemia was incomplete, with signs of permanent failure of energy metabolism. There was persistent ATP reduction proportional to the duration of the hypoglycemia. The short-term recovery of EEG and sensory evoked responses was proportional to the duration of severe hypoglycemia. The neurophysiological recovery after 5 min of severe hypoglycemia was complete. After 30 min of severe hypoglycemia, the evoked responses recovered but showed a significant prolongation of latency, compared with normal. After 60 min of severe hypoglycemia, no early evoked response and scanty EEG activity were observed. The neurophysiological observations indicate a persistent deficit of synaptic transmission in the somatosensory pathway, including the cortical projection. This can be correlated with neuropathologic changes that are particularly prominent in intermediate cortical layers, as previously shown.
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| 4. |
- Lundgren, Johan, et al.
(författare)
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Acidosis-induced ischemic brain damage: are free radicals involved?
- 1991
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 11:4, s. 587-596
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Tidskriftsartikel (refereegranskat)abstract
- Substantial evidence exists that reactive oxygen species participate in the pathogenesis of brain damage following both sustained and transient cerebral ischemia, adversely affecting the vascular endothelium and contributing to the formation of edema. One likely triggering event for free radical damage is delocalization of protein-bound iron. The binding capacity for some iron-binding proteins is highly pH sensitive and, consequently, the release of iron is enhanced by acidosis. In this study, we explored whether enhanced acidosis during ischemia triggers the production of reactive oxygen species. To that end, enhanced acidosis was produced by inducing ischemia in hyperglycemic rats, with normoglycemic ones serving as controls. Production of H2O2, estimated from the decrease in catalase activity after 3-amino-1,2,4-triazole (AT) administration, was measured in the cerebral cortex, caudoputamen, hippocampus, and substantia nigra (SN) after 15 min of ischemia followed by 5, 15, and 45 min of recovery, respectively (in substantia nigra after 45 min of recovery only). Free iron in cerebrospinal fluid (CSF) was measured after ischemia and 45 min of recovery. Levels of total glutathione (GSH + GSSH) in cortex and hippocampus, and levels of alpha-tocopherol in cortex, were also measured after 15 min of ischemia followed by 5, 15, and 45 min of recovery. The results confirm previous findings that brief ischemia in normoglycemic animals does not measurably increase H2O2 production in AT-injected animals. Ischemia under hyperglycemic conditions likewise failed to induce increased H2O2 production. No difference in free iron in CSF was observed between animals subjected to ischemia under hyper- and normoglycemic conditions. The moderate decrease in total glutathione or alpha-tocopherol levels did not differ between normo- and hyperglycemic animals in any brain region or at any recovery time. Thus, the results failed to give positive evidence for free radical damage following brief periods of ischemia complicated by excessive acidosis. However, it is possible that free radical production is localized to a small subcellular compartment within the tissue, thereby escaping detection. Also, the results do not exclude the possibility that free radicals are pathogenetically important after ischemia of longer duration.
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