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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In models of cerebral ischemia, it is important to rigidly control brain glucose in the peri-ischemic period because alterations in brain glucose can affect the severity of the postischemic injury. The following study evaluated the effect of a continuous glucose infusion as a means of producing stable increases in brain glucose that could be monitored by measuring either blood or plasma glucose. Fifty-four halothane-anesthetized rats were studied. Rats received either no treatment (control group; N = 6), saline 2 ml/h (N = 24), or glucose 1 g/kg per h in saline 2 ml/h (N = 24). In the latter two groups, samples of blood, plasma, and brain glucose were obtained at either 30, 60, 120, or 180 min of the infusion (N = 6 per group per sample period). Saline infusion had no effect on either blood, plasma, or brain glucose. In contrast, glucose infusion produced a significant increase in all three variables, achieving plateau increases during the 60-180 min measurement periods [blood glucose = 197 +/- 20 mg/dl (mean +/- S.D.) at 60 min, 220 +/- 34 mg/dl at 120 min, and 217 +/- 22 mg/dl at 180 min versus control blood glucose = 89 +/- 10 mg/dl]. Regardless of the treatment group, there was excellent correlation between blood and plasma glucose (r = 0.99; P much less than 0.001), blood and brain glucose (r = 0.96; P much less than 0.001), and plasma and brain glucose (r = 0.97; P much less than 0.001). The authors conclude that continuous glucose infusions are an effective method to produce stable increases in brain glucose in experimental models; and, in contrast to other methods for achieving brain glucose increases, the brain glucose increases can be accurately assessed by measuring blood or plasma glucose.
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PMID:The effects of continuous glucose infusion on blood, plasma, and brain glucose in anesthetized rats. 165 95

Experimental and clinical studies have revealed a worsened neurologic outcome after cerebral ischemia in hyperglycemic subjects, including hyperglycemic diabetic subjects. A possible therapy to reduce the magnitude of ischemic brain injury in diabetic subjects would be to use an insulin infusion to reduce brain glucose concentrations to values found in those who are normoglycemic and non-diabetic. The present study, using hyperglycemic diabetic rats, examined the effect of an insulin infusion on plasma and brain glucose concentrations to determine their relationship while plasma glucose concentrations decreased. In addition, plasma and brain glucose concentrations were compared to those in diabetic and nondiabetic rats treated with saline. Saline had no effect on the plasma or brain glucose concentrations in the diabetic rats or nondiabetic rats. The saline-treated diabetic rats had increased plasma and brain glucose concentrations as well as an increased brain-to-plasma glucose ratio when compared to the saline-treated nondiabetic rats. When an insulin infusion was used in diabetic rats to decrease plasma glucose to nondiabetic levels over approximately 2 h, the brain glucose concentration decreased. However, the brain-to-plasma glucose ratio remained at the "diabetic" value, so that the brain glucose concentration tended to remain increased when compared to normoglycemic, nondiabetic rats. We conclude that if these results are applicable to humans, measurement of plasma glucose in diabetic patients will underestimate the amount of glucose in the brain and this relationship will not be influenced by acute insulin therapy.
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PMID:The effects of insulin infusion on plasma and brain glucose in hyperglycemic diabetic rats. A comparison with placebo-treated diabetic and nondiabetic rats. 192 77

The opioid receptor antagonist nalmefene improves cellular bioenergetics and attenuates the reduction in tissue glutamate levels after global cerebral ischemia/reperfusion. The latter finding suggests that nalmefene might inhibit glutamate release during ischemia. To test this hypothesis, we used microdialysis techniques to examine the effect of nalmefene pretreatment on extracellular excitatory amino acid levels during global cerebral ischemia in rats. Saline, (-)-nalmefene (20, 100 or 500 micrograms/kg) or the inactive nalmefene enantiomer (+)-nalmefene (100 micrograms/kg) were given 15 min prior to induction of ischemia using a multi-vessel occlusion model. Pretreatment with (-)-nalmefene decreased peak dialysate glutamate in a dose-dependent fashion as compared to saline-treated controls, whereas (+)-nalmefene had no effect. These results suggest that opioid receptors may modulate glutamate release during ischemia and that inhibition of excitatory amino acid release may contribute to the protective actions of opioid receptor antagonists in cerebral ischemia.
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PMID:Opioid receptor antagonist nalmefene stereospecifically inhibits glutamate release during global cerebral ischemia. 790 1

Using the middle cerebral artery occlusion model, we studied the effects of Zuzhongping on experimental focal cerebral ischemia. Twenty-eight adult male Wistar rats were randomly divided into three groups: (1) Zuzhongping group (n = 9), (2) Saline control group (n = 10), and (3) Blank control group (n = 9). Group 1 and group 2 received via a gastric tube 1 1ml/kg/day of Zuzhongping and normal saline, respectively. The cerebral middle arteries on the right side of 28 rats were occluded with a bipolar electro-coagulater at sites 1-2 mm from the right olfactory nerve tract. Ischemic volumes were measured by an image analytic system when the cerebral ischemia had lasted 24 h. The results showed that the ischemic volume of Zuzhongping group was significantly smaller than that of group 2 and group 3, suggesting a protective effect of Zuzhongping.
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PMID:[Effects of zuzhongping on ischemic volume in the rat model of middle cerebral artery occlusion]. 807 Jul 59

The concentrations of amino acids (AA), stroke index and infarct area were determined in 26 gerbils which were divided into 3 groups: RSM-treated (n = 8), Saline-treated (n = 10) and sham-operated (n = 8). The levels of AA were measured with microdialysis technique in cerebral cortex. The concentrations of neurotransmitter AA, as Glu and GABA and Asp, were significantly increased during the first 60 min after CCA ligation, while the concentrations of non-neurotransmitter AA, as Thr and Ser, had no significant changes. In RSM-treated gerbils, the level of Glu was significantly lower than that of the saline-treated, but the GABA in RSM-treated was significantly higher than that of the saline-treated. The ratio of Glu/GABA was significantly decreased after ischemia. The RSM could improve the reduction of ratio of Glu/GABA during 0-30 min and 91-120 min after cerebral ischemia. There were statistically significant decrease in terms of stroke index in RSM-treated group when compared with saline-treated group at 24 h and 16 h after CCA ligation respectively. The RSM has a tendency to decrease the size of infarct area, but no statistical difference. The results suggest that the neurotransmitter AA involve in the pathophysiological procedures of cerebral ischemia and the RSM can attenuate dysfunctions of EAA and IAA. Furthermore, the results also imply that there may be an alternate way to treat cerebral ischemia by inhibiting the presynaptic releasing of Glu and stimulating the releasing of GABA.
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PMID:Effect of radix salviae miltiorrhizae on EAA and IAA during cerebral ischemia in gerbils: a microdialysis study. 819 18

The effect of treatment with the Ca2+ channel blocker and 5-HT2 receptor antagonist levemopamil (recommended INN for (S)-emopamil) on the extent of ischaemic brain oedema was studied by magnetic resonance imaging in vivo. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent middle cerebral artery occlusion. The treatment consisted of slow intravenous injections of an aqueous solution of levemopamil given immediately after middle cerebral artery occlusion and again 2 h and 4 h later. One group of animals (n = 17) received 3 x 2 mg/kg of levemopamil (total dose: 6 mg/kg) and another group (n = 13) received 3 x 4 mg/kg (total dose: 12 mg/kg). Saline was administered to the controls (n = 16) at corresponding times. High-resolution T2-weighted spin echo images were obtained 24 h after middle cerebral artery occlusion from two transversal brain planes (4.5 mm and 6.5 mm dorsal to the interaural line). Dose-dependent reductions of brain oedema were achieved in both brain planes. The lower dose of levemopamil reduced the extent of oedema significantly (P < 0.05) by 20 +/- 3.7% in the upper and by 21 +/- 3.8% in the lower brain plane as compared to the controls (means +/- S.E.M.). The higher dose diminished the extent of oedema in the same planes by 30 +/- 3.5% and 31 +/- 4.0%, respectively. Dose-dependent reductions of infarct size, as determined by vital tissue staining using 2,3,5-triphenyltetrazolium chloride (TTC), were observed in the levemopamil-treated groups. Body temperature was not affected by levemopamil, suggesting direct cerebroprotection by this drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging. 820 18

Alcohol was infused intravenously into chronically cannulated adult female sheep as a 40% solution (w/v) at doses of 0.5, 1.0, 1.5, or 2.0 g/kg over 1 hr. Saline infusions, equal in volume to the highest dose, served as a control. Dose-dependent peak blood alcohol concentrations (BACs) were attained 60 min after the beginning of alcohol infusion for all doses (86.5 +/- 3.7, 213.2 +/- 11.0, 373.2 +/- 14.3, and 494.1 +/- 34.5 mg/dl +/- SE, respectively). Plasma cortisol concentrations increased in response to the 0.5 g/kg infusions (BACs less than 100 mg/dl), whereas both ACTH and cortisol concentrations increased in the 1.0 and 2.0 g/kg dose groups. Mean arterial pressure, heart rate, and Paco2 increased, whereas Pao2 decreased in response to the 1.5 and 2.0 g/kg infusions. Arterial pH declined in the highest dose group. Respiratory rate was lower in all groups receiving alcohol compared with that of the control group. Hematocrit did not change. We conclude that BACs in adult female sheep below 100 mg/dl (levels easily achieved by social drinkers) result in activation of the hypothalamus-pituitary-adrenal axis. At high BACs (> 350 mg/dl), pituitary adrenal responses are accompanied by increases in heart rate, blood pressure, and Paco2 and decreases in Pao2 and arterial pH. These findings support the hypothesis that alcohol acts directly on the brain to mediate pituitary adrenal responses and that the additional responses to high BACs (the blood gas and hemodynamic responses), might be mediated by direct actions of alcohol on the brain, by cerebral ischemia, or by alcohol-mediated suppression of ventilatory drive and hypoxemia.
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PMID:Acute hemodynamic, pituitary, and adrenocortical responses to alcohol in adult female sheep. 898 21

Antioxidant enzymes such as superoxide dismutase (SOD) have shown neuroprotective effects in animal models of cerebral ischemia, but only at very high doses. Modifications to increase the plasma half-life or blood-brain barrier (BBB) permeability of SOD have resulted in limited neuroprotective effects. No one has demonstrated neuroprotection with postischemic administration. The specific aim of the present study was to administer systemically a polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, following global cerebral ischemia in rats and analyze the effects on the selective vulnerability of CA1 hippocampal neurons. Following 12 min of four-vessel occlusion, global cerebral ischemia, male Wistar rats were dosed (i.v.) with either saline, native SOD (5000 U/kg), polyamine-modified SOD (5000 U/kg), or enzymatically inactive, polyamine-modified SOD (2.1 mg/kg) twice daily for 3 days. Neuroprotective effects on hippocampal CA1 neurons were assessed using standard histological methods. Saline-treated animals had very few remaining CA1 neurons (1.44 +/- 0.60 neurons/reticle; x +/- S.E.M.) compared to sham rats (58.57 +/- 0.69). Native (10.38 +/- 2.96) or inactive, polyamine-modified SOD (7.32 +/- 2.68) did not show significant neuroprotective effects. Polyamine-modified SOD, however, resulted in the survival of significantly more CA1 neurons (24.61 +/- 5.90; P < 0.01). Postischemic, systemic administration of polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, significantly reduced hippocampal CA1 neuron loss following global cerebral ischemia. Similar modification of other antioxidant enzymes and neurotrophic factors with polyamines may provide a useful technique for the systemic delivery of therapeutic proteins across the BBB for the treatment of stroke and other neurodegenerative disorders.
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PMID:Postischemic, systemic administration of polyamine-modified superoxide dismutase reduces hippocampal CA1 neurodegeneration in rat global cerebral ischemia. 913 58

Saline and indocyanine green dye were the first agents noted to produce a contrast effect when injected peripherally during M-mode echocardiographic imaging, although it was subsequently found that almost any type of injected solution would have this effect. These first-generation contrast agents were limited to opacification of right heart structures, and they prompted subsequent development of agents that traverse pulmonary circulation. Although opacification limited to right heart structures is considered a limitation of these first-generation agents, this is an advantage when attempting to identify the presence of right-to-left shunt. First-generation air contrast is considered the gold standard for identification of patent foramen ovale (PFO). However, PFO investigators have used varying criteria to define abnormal contrast studies. There are also multiple mechanisms by which saline contrast studies may produce both false-positive and false-negative results for presence of PFO. There is mounting experimental evidence that PFO is associated with cerebral ischemia and migraine headache, with a resulting evolution of devices for percutaneous closure of these shunts. Echocardiographic physicians must be aware of potential pitfalls of the air contrast technique to avoid exposing patients to unnecessary risk of closure devices, and missing the potential benefit of shunt closure in appropriately selected patients.
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PMID:A critical review of patent foramen ovale detection using saline contrast echocardiography: when bubbles lie. 1645 28

Thrombolysis with tissue plasminogen activator (tPA) is the only pharmacotherapy available for cerebral ischemia. However, the use of tPA can increase the risk of hemorrhage due to blood-brain barrier (BBB) breakdown. Recent evidence suggests that increased activation of matrix metalloproteinases (MMPs) may be involved in this breakdown. This study examines the temporal profile of MMP-2 and -9 following tPA administration to ischemic rats. Male Sprague-Dawley rats were randomly assigned to one of four groups (Sham-tPA; Sham-Saline; Ischemia-tPA; Ischemia-Saline; group n = 6, total N = 120). Focal embolic ischemia was induced by middle cerebral artery occlusion through injection of an autologous clot. One hour post-surgery, tPA (10 mg/kg) or saline was delivered intravenously and animals were euthanized at 3, 6, 12, or 24 h after onset of ischemia. Infarct volume was measured by TTC staining; BBB components examined immunohistochemically; and MMP activation measured by gelatin zymography. Our results show that tPA significantly reduced infarct volumes (overall infarct volume-Sham-tPA: 5.80 +/- 4.55 [mean +/- SE]; Sham-Saline: 5.00 +/- 4.23; Ischemia-tPA: 186.1 +/- 73.45; Ischemia-Saline: 284.8 +/- 88.74; all P < 0.05). Treatment with tPA was also associated with the activation of MMP-9 at 6, 12, and 24 h following ischemia. No temporal changes were observed in MMP-2 activation, although tPA administration increased its activity compared to saline treatment. Analyses of immunohistochemistry showed that destruction of components of the BBB followed MMP-9 activation. Thus, increased MMP-9 activation may, in part, be responsible for the increases in hemorrhagic transformation reported with use of tPA. Our study is the first to demonstrate the temporal profile of MMP activation following thrombolysis with tPA in a model of thrombotic focal cerebral ischemia.
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PMID:Matrix metalloproteinase activation and blood-brain barrier breakdown following thrombolysis. 1662 94


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