Methods: Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques.
Results: Before ischemia, D rats had greater concentrations of brain glucose (12.18+/-2.67 micro mol/g) than did either ID (5.10 +/-1.33) or ND (3.20+/-0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/-0.28) than in either ID (0.29+/-0.09) or ND (0.36 +/-0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups. 相似文献
Methods: Fifty-eight halothane-anesthetized (1.3% inspired) Sprague-Dawley rats were assigned randomly to be administered either no treatment (N = 18) or 2 mg/kg intraperitoneal dexamethasone (N = 40). The latter were administered dexamethasone 3 h before the study only (N = 8) or for 3 h before the study plus daily for 1 day (N = 8), 2 days (N = 8), or 4 days (N = 16). Of the rats treated with dexamethasone for 4 days, one half (N = 8) were administered an insulin-containing saline infusion subsequently to restore normoglycemia short-term. All other rats (N = 50) were administered an infusion of saline without insulin. Plasma glucose was quantified, and brains were excised after in situ freezing. Brain glucose and glycogen concentrations were measured using enzymatic fluorometric analyses.
Results: After 4 days of dexamethasone treatment, plasma glucose was 159% greater than in rats administered placebo (i.e., 22.01 +/- 4.66 vs. 8.51 +/- 1.65 [mu]mol/ml; mean +/- SD;P < 0.0001). Brain glucose concentrations increased parallel to plasma glucose. An insulin infusion for 27 +/- 5 min restored normoglycemia but resulted in a brain-to-plasma glucose ratio that was 32% greater than baseline values (P < 0.01). Neither dexamethasone nor the combination of dexamethasone plus insulin affected brain glycogen concentrations. 相似文献
Methods: For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mmHg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 [micro sign]g [middle dot] kg-1 [middle dot] h-1) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia.
Results: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P < 0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P < 0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43 +/- 22% vs. 87 +/- 10%; P < 0.001). Trimethaphan abolished the beneficial effects of isoflurane (91 +/- 6%; P < 0.001). Similar observations were made in the cortex. 相似文献
Background/Aims
Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R. 相似文献Methods: Unilateral CSD was induced by application of KCl to the frontal cortex (CSD hemisphere) in three groups of isoflurane-anesthetized rats (CSD groups; n = 8/group). Sham animals (n = 12) did not undergo CSD. In a fifth group (n = 8), ketamine was administered during KCl application to inhibit CSD. One, three, or seven days after CSD, animals were subjected to forebrain ischemia produced by bilateral carotid artery occlusion. Injury to the striatum, hippocampus, and cortex was evaluated in hematoxylin and eosin-stained brain sections 3 days after ischemia.
Results: Preischemic CSD reduced postischemic injury in the ipsilateral cortex. The ratio of the number of injured neurons in the CSD hemisphere to that in the non-CSD hemisphere was significantly less in the groups subjected to CSD 1 day (0.51 +/- 0.33), 3 days (0.56 +/- 0.22), and 7 days (0.40 +/- 0.17) before ischemia than in the sham operated group (1.11 +/- 0.47). In the ketamine group (CSD inhibition), there were no differences in the extent of injury in the two hemispheres (ratio = 0.84 +/- 0.47). Injury to the striatum and hippocampus was similar among the groups. Within each group, injury to these subcortical structures in the CSD hemisphere was not different from that in the non-CSD hemisphere. 相似文献
Methods: Microdialysis probes were implanted into the parietal cortex and dorsal hippocampus of four groups of anesthetized rats (n = 5 per group). The hypothermic group was anesthetized with 1.2% halothane. The two isoflurane groups were anesthetized with 0.5 minimum alveolar concentration or electroencephalographic burst-suppression doses of isoflurane ([nearly equal] 2 minimum alveolar concentration). The control group was anesthetized with 70% N2 O-30% Oxygen2 and fentanyl. The pericranial temperature was maintained at 34 degrees Celsius in the hypothermic group and at 38 degrees Celsius in the remaining groups. Ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension to 35 mmHg for 10 min, followed by a reperfusion period of 70 min. Dialysate was collected before, during, and after ischemia. The concentrations of glutamate and glycine in the dialysate were measured by high-performance liquid chromatography.
Results: Preischemic glutamate and glycine concentrations in the dialysate were similar among the groups. Ischemia resulted in a significant increase in glutamate and glycine concentrations in the N sub 2 O-fentanyl groups in the parietal cortex and in the hippocampus. This increase in neurotransmitter concentrations did not occur in the hypothermic group in either structure. Isoflurane reduced glutamate concentrations in both structures and glycine concentrations in the hippocampus. In the parietal cortex, glycine concentrations did not increase in either isoflurane group. 相似文献
Methods: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25[mu]g [middle dot] kg-1 [middle dot] h-1 [middle dot] 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion.
Results: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. 相似文献
Methods: Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later.
Results: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0.023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0.935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration. 相似文献
Methods: Rats were subjected to 10 min of near-complete forebrain ischemia while anesthetized with either 1.4% isoflurane or 70% nitrous oxide-fentanyl. Neurologic and histologic outcomes were measured at 5 days, 3 weeks, or 3 months after ischemia.
Results: At 5 days, isoflurane-anesthetized rats had less damage than did fentanyl-nitrous oxide-anesthetized rats (mean +/- SD, percent alive hippocampal CA1 neurons = 58 +/- 29 vs. 20 +/- 16, respectively; P = 0.011). This was accompanied by improved motor function in the isoflurane group (P = 0.002). At 3 weeks, there was no difference between groups for either outcome variable (percent alive CA1 neurons = 35 +/- 26 and 36 +/- 28 for isoflurane and fentanyl-nitrous oxide, respectively). Similarly, at 3 months, there was no difference between groups (percent alive CA1 neurons = 56 +/- 27 and 60 +/- 27 for isoflurane and fentanyl-nitrous oxide, respectively). Morris water maze performance at 3 months was similar between anesthetic groups and was also similar to sham performance. The percent alive CA1 neurons in the fentanyl-nitrous oxide group increased with duration of recovery (P = 0.004). There were no differences among isoflurane groups over time (5 days vs. 3 weeks, P = 0.26; 5 days vs. 3 months, P = 0.99; 3 week vs. 3 months, P = 0.32). 相似文献
Methods: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 [degree sign]C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 [degree sign]C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 [degree sign]C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde.
Results: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 [degree sign]C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 [degree sign]C. Fifteen minutes of immediate cooling (27 [degree sign]C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 [degree sign]C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling. 相似文献
OBJECTIVE
Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in sensory neurons is due to abnormal mitochondrial respiratory function.RESEARCH DESIGN AND METHODS
Rates of oxygen consumption were measured in mitochondria from dorsal root ganglia (DRG) of 12- to- 22-week streptozotocin (STZ)-induced diabetic rats, diabetic rats treated with insulin, and age-matched controls. Activities and expression of components of mitochondrial complexes and reactive oxygen species (ROS) were analyzed.RESULTS
Rates of coupled respiration with pyruvate + malate (P + M) and with ascorbate + TMPD (Asc + TMPD) in DRG were unchanged after 12 weeks of diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31–44% and with Asc + TMPD by 29–39% compared with control. Attenuated mitochondrial respiratory activity of STZ-diabetic rats was significantly improved by insulin that did not correct other indices of diabetes. Activities of mitochondrial complexes I and IV and the Krebs cycle enzyme, citrate synthase, were decreased in mitochondria from DRG of 22-week STZ-diabetic rats compared with control. ROS levels in perikarya of DRG neurons were not altered by diabetes, but ROS generation from mitochondria treated with antimycin A was diminished compared with control. Reduced mitochondrial respiratory function was associated with downregulation of expression of mitochondrial proteins.CONCLUSIONS
Mitochondrial dysfunction in sensory neurons from type 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS.Peripheral nerves of diabetic patients develop a spectrum of pathology that can take many years to emerge (1,2). Experimental studies over shorter time periods have demonstrated that hyperglycemia can induce cellular damage through increased glucose metabolism by aldose reductase (3), elevated protein glycation (4), and increased mitochondrial NADH supply, which enhances electron availability causing partial reduction of oxygen to superoxide radicals in the proximal part of the electron transport chain (5,6). These three mechanisms may combine to trigger large elevations in reactive oxygen species (ROS) that induce oxidative stress and tissue damage (7–9). The ability of nerves to survive oxidative stress may also be impaired in diabetes because of suboptimal trophic support from insulin, insulin-like growth factors, and neurotrophic factors (10,11).Although increased oxidative stress has become a widely accepted consequence of hyperglycemia in models of diabetic neuropathy, the source of excessive ROS is not defined. Mitochondria are one plausible source of ROS, based on reports of an acute glucose-induced elevation of flux through the electron transport chain in endothelial cells that was accompanied by hyperpolarization of the mitochondrial inner membrane and subsequent stimulation of ROS generation in the proximal aspect of the electron transport chain (5,6). However, this mechanism may not extend to other cell types or to longer durations of diabetes, since mitochondrial respiration and enzymatic activities are reduced in mitochondria from streptozotocin (STZ)-induced diabetic rat hearts (12,13), and activity of the mitochondrial electron transport chain and citrate synthase are decreased in skeletal muscle of patients with type 2 diabetes (14–16). Further, we and others have measured depolarization, rather than hyperpolarization, of the mitochondrial inner membrane in acutely isolated adult DRG sensory neurons from STZ-diabetic rats that can be corrected by treatment with neurotrophin-3 or insulin at doses that did not affect hyperglycemia (17–19). Given the unclear understanding of the contribution of mitochondrial-derived ROS to neuronal oxidative stress, we have now directly measured rates of activity within the mitochondrial respiratory chain and ROS production in neurons from STZ-diabetic rats. 相似文献Methods : A questionnaire was mailed to 44 men who had undergone radical prostatectomy for prostate cancer at a mean age of 65.5 years and were free from recurrent symptoms at a mean follow-up of 3.3 years. Most (70%) had pathologic stage C or Dl disease and many (86%) had received adjuvant endocrine therapy. After reporting urinary symptoms, the patients estimated their overall urinary, sexual, physical, psychological, and social functioning, and global satisfaction level with their treatment outcome. Regression analysis was performed to detect significant factors in predicting overall urinary conditions or satisfaction.
Results : Daily urinary leakage and forceless urinary stream was noted in 30% and 23% of patients, respectively. Overall urinary conditions were evaluated as good or very good in 61 % of patients, and were most significantly associated with the patient's satisfaction with their force of urinary flow (P< 0.001). Global satisfaction with treatment outcome was estimated as good or very good in 80% of patients, and it was predicted by physical functions (P = 0.01 3) and psychological distress (P = 0.036), and to a lesser extent by urinary conditions (P = 0.1 95).
Conclusion : A forceless urinary stream was the most significant determinant for overall urinary conditions in patients who had a radical prostatectomy. Global satisfaction with treatment outcome was only marginally affected by urinary conditions. PhysicaUunction and psychological distress were major factors affecting the satisfaction level in this population. 相似文献