| 1. |
- Deshpande, J. K., et al.
(författare)
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Amelioration of ischaemic brain damage by postischaemic treatment with flunarizine
- 1985
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Ingår i: Neurological Research. - : Informa UK Limited. - 0161-6412 .- 1743-1328. ; 7:1, s. 27-29
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Tidskriftsartikel (refereegranskat)abstract
- The effect of flunarizine, a calcium entry blocker, on ischaemic damage was investigated using a new model of forebrain ischaemia. Fasted rats were subjected to nine minutes ischaemia and one week recovery. One group served as control; a second was pretreated orally with flunarizine; a third group received postischaemic flunarizine treatment Focussing on the hippocampus, an area of high susceptibility to ischaemic damage, we report that flunarizine treatment significantly reduced neuronal necrosis. Importantly, the amelioration of necrosis was also observed when flunarizine was administered 5 min following resumption of cerebral perfusion.
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| 2. |
- Deshpande, J. K., et al.
(författare)
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Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia
- 1987
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 7:1, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- The present study was undertaken to correlate calcium accumulation with the development of neuronal necrosis following transient ischemia. After 10 min of forebrain ischemia in the rat—a period that leads to reproducible damage of CA1 pyramidal cells—determination of calcium concentration and evaluation of morphological signs of cell body necrosis in the dorsal hippocampus were performed at various recirculation times. Tissue calcium concentration was not different from control at the end of ischemic period and did not change after 3, 6, 12, or 24 h of recirculation. However, after 48 h, calcium content increased significantly, with a further increase being seen after 72 h. At early recovery periods, only scattered necrotic neurons were observed. after 48 h, only 2 of 12 hemispheres showed more than 25 necrotic cells per section. More conspicuous neuronal death was observed after 72 h. The results thus demonstrate that net accumulation of calcium in regio superior of the hippocampus precedes marked necrosis of CA1 pyramidal cells. The results suggest that one primary event in the delayed death of these cells is membrane dysfunction with increased calcium cycling.
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| 3. |
- Deshpande, J. K., et al.
(författare)
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Flunarizine, a calcium entry blocker, ameliorates ischemic brain damage in the rat
- 1986
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Ingår i: Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 0003-3022. ; 64:2, s. 215-224
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Tidskriftsartikel (refereegranskat)abstract
- The effects of flunarizine, a calcium entry blocker, were evaluated in a long-term survival model of ischemia in rats. One group of animals received the drug orally at 24 and 4 h prior to the insult (40 mg·kg-1·dose-1). Another group was given flunarizine following the insult, intravenously at 5 min (0.1 mg·kg-1), and orally at 8 and 24 h (40 mg·kg-1·dose-1). A third group received the solvent for the oral suspension on the same schedule as the pretreated group. Six animals from each group were subjected to 9 min ischemia and recovery of 7 days, at which time the brains were harvested for histologic study. In another six animals from each group, cortical metabolites and fatty acids were determined during early recirculation. Local cerebral blood flow was measured at 60 min recirculation in a third set of animals. Flunarizine significantly improved histological outcome (fewer irreversibly damaged cells) in both treatment groups. This amelioration was not related to improvement of cerebral blood flow during the period of delayed hypoperfusion, nor the postischemic levels of high-energy phosphates or free fatty acids.
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| 4. |
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| 5. |
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| 6. |
- Warner, D. S., et al.
(författare)
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The effect of isoflurane on neuronal necrosis following near-complete forebrain ischemia in the rat
- 1986
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Ingår i: Anesthesiology. - : Ovid Technologies (Wolters Kluwer Health). - 0003-3022. ; 64:1, s. 19-23
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Tidskriftsartikel (refereegranskat)abstract
- The effect of deep isoflurane anesthesia on ischemically induced neuronal damage was evaluated in the rat. Sixteen mechanically ventilated animals were maintained normocapnic and normothermic while subjected to a near complete forebrain ischemia insult induced with systemic hypotension (MAP = 50± mmHg) and bilateral carotid artery occlusion. Prior to ischemia, eight of the rats received isoflurane by inhalation until the EEG demonstrated a burst suppression pattern; the other eight were untreated controls. After 10 min of ischemia, the carotid clamps were removed, blood pressure was restored, and, in the treated group, isoflurane administration discontinued. Following the ischemic insult, the animals were observed over a 7-day period, at which time they were killed and the brains prepared for histologic study. Severity of damage was assessed by a direct count of irreversibly damaged neurons, which appear bright red when stained with cresyl violet-acid fuchsin. Areas of particular interest were those that characteristically display vulnerability to ischemic damage, i.e., hippocampus, caudate nuclei, and neocortex. The control group revealed severe damage in the hippocampal CA1 sector (70% cells acidophilic) with more variability in the caudate nuclei and neocortex. The treated group showed a similar extent of damage with approximately 74% cells acidophilic in hippocampus (CA1). Clinical appearance was indistinguishable between groups. The authors conclude that pretreatment with isoflurane shows no beneficial effects on delayed neuronal necrosis following near-complete forebrain ischemia.
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| 7. |
- Westerberg, E., et al.
(författare)
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Regional differences in arachidonic acid release in rat hippocampal CA1 and CA3 regions during cerebral ischemia
- 1987
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 7:2, s. 189-192
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the levels of arachidonic acid during ischemia in selectively vulnerable areas of the hippocampus were studied in the rat brain. Since neurons in the CA1 region are more vulnerable to ischemia than neurons in the adjacent CA3 region, the release of arachidonic acid in these two regions was measured during decapitation ischemia of 4- to 12-min duration. The concentration of free arachidonic acid increased with the duration of ischemia in both regions. However, the level was significantly higher in CA1 than in CA3 after 8 and 12 min of ischemia. This difference in arachidonic acid accumulation may reflect differences between the regions in agonist-dependent phospholipid breakdown as well as calcium-dependent phospholipase activity. The importance for the development of neuronal necrosis is discussed.
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