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

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-D-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 +/- 15.8 microM (mean +/- SD) to 21.4 +/- 11.4 microM (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 +/- 5.8 to 19.9 +/- 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.
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PMID:A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia. 779 Apr 9

Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17 beta-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17 beta-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 +/- 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 +/- 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 +/- 1 and 9 +/- 2 ml min-1 100 g-1, respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 +/- 27 and 183 +/- 27 ml min-1 100 g-1. However, EFEM experienced higher CBF during ischemia (e.g., 13 +/- 2 ml min-1 100 g-1) and less hyperemia (134 +/- 4 ml min-1 100 g-1 in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17 beta-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal.
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PMID:Postischemic cerebral blood flow recovery in the female: effect of 17 beta-estradiol. 779 Apr 16

We determined the effect of 4-5 weeks of diabetes on ATP recovery following global incomplete cerebral ischemia. 31P magnetic resonance spectra of ATP, intracellular pH (pHi), and CBF (radiolabeled microspheres) were measured in three groups of anesthetized dogs (n = 8/group): chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose of > 10 mM for 4-5 weeks); acute hyperglycemia (blood glucose of > 10 mM) during ischemia and reperfusion in nondiabetic dogs; and normoglycemic controls. Twenty minutes of incomplete ischemia was produced by ventricular fluid infusion to keep cerebral perfusion pressure (CPP) at 10 mm Hg during spontaneous variations in MABP. Intracranial pressure was increased initially to similar levels, resulting in a similar Cushing response among the groups. However, during the final 8 min of ischemia, MABP decreased to a greater extent in diabetic (86 +/- 42 mm Hg) than in hyperglycemic (162 +/- 30 mm Hg) and normoglycemic (135 +/- 54 mm Hg) groups and remained lower throughout 3 h of reperfusion. CPP was kept constant during ischemia, but was lower throughout reperfusion in diabetic dogs. During ischemia CBF was reduced similarly among groups: 5 +/- 3 ml.min-1 x 100 g-1 in hyperglycemic and normoglycemic and 4 +/- 3 ml.min-1 x 100 g-1 in diabetic dogs. During reperfusion early hyperemia was attenuated and delayed hypoperfusion was augmented (7 +/- 17 ml.min-1 x 100 g-1 by 180 min) as a result of low perfusion pressure in diabetics. However, medullary blood flow was similar among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Poor hemodynamic and metabolic recovery after global incomplete cerebral ischemia associated with short-term diabetes in dogs. 779 Apr 17

Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglycemia, pretreatment with the 21-aminosteroid tirilazad mesylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg/kg plus 0.2 mg/kg/h; n = 8) or vehicle (n = 8). Hyperglycemia (400-500 mg/dl) was produced prior to 30 min of global incomplete cerebral ischemia. Intracellular pH and high energy phosphates were measured by phosphorus magnetic resonance spectroscopy. During ischemia, microsphere-determined CBF decreased to 8 +/- 4 ml min-1 100 g-1 and intracellular pH decreased to 5.6 +/- 0.2 in both groups. During the first 20 min of reperfusion, ATP partially recovered in the vehicle group to 57 +/- 21% of baseline, but then declined progressively in association with elevated intracranial pressure. By 30 min, ATP recovery was greater in the tirilazad group (77 +/- 35 vs. 36 +/- 19%), although postischemic hyperemia was similar. By 45 min, the tirilazad group had a higher intracellular pH (6.5 +/- 0.5 vs. 5.9 +/- 0.6) and a lower intracranial pressure (18 +/- 6 vs. 52 +/- 24 mm Hg). By 180 min, blood flow and ATP were undetectable in seven of eight vehicle-treated dogs, whereas ATP was > 67% and pH was > 6.7 in six of eight tirilazad-treated dogs. Thus, tirilazad acts during early reperfusion to prevent secondary metabolic decay associated with severe acidotic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tirilazad pretreatment improves early cerebral metabolic and blood flow recovery from hyperglycemic ischemia. 779 42

We have previously reported reduction in EEG activity in preterm babies after tracheal instillation of Curosurf. To elucidate the cause of EEG depression, we have examined cerebral blood flow (CFB), amplitude-integrated EEG (aEEG), mean arterial blood pressure (MABP) and plasma hypoxanthine (Hx) concentration in a group of preterm babies before and immediately after administration of surfactant. No change occurred in CBF immediately after surfactant treatment despite a significant decrease in MABP. At 60 min after surfactant administration, a significant reduction in CBF occurred (p < 0.05). However, when CBF values were corrected for changes in PaCO2, no reduction in CBF was observed. Mean plasma Hx concentration was 11.6 (SD 7.3) mumol/l before surfactant therapy, which decreased significantly to 8.1 (5.8) mumol/l (p < 0.05) 15-30 min after treatment. No correlations were found between plasma Hx concentration and FiO2, a/A pO2, PaCO2, SaO2, arterial blood pressure, CBF or the degree of EEG depression. This study indicates that EEG depression observed after surfactant instillation is not caused by cerebral ischemia.
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PMID:Cerebral blood flow and plasma hypoxanthine in relation to surfactant treatment. 781 84

Monitoring of ICP from the subarachnoid, intraparenchymal, or ventricular spaces can be accomplished easily and reliably. The risks and benefits of each approach should be considered when choosing the monitoring technique. The goal of ICP management is to prevent herniation and to optimize cerebral perfusion. Even transient episodes of post-traumatic cerebral ischemia due to inadequate CPP can quickly nullify all resuscitative efforts. The provision of sufficient CBF is complicated by the varying degree of disruption of pressure autoregulation commonly resulting from head trauma. Post-injury, there is a need to provide a CPP which is elevated to some extent with respect to that sufficient in uninjured brains. This generally requires a CPP of at least 70 mm Hg, which must be accomplished by maintaining an adequate MAP while controlling ICH. Although ICH can generally be controlled using methods commonly employed, the majority of these techniques have potential complications. Additionally, there is increasing evidence that significant variation exists in the pathologic processes driving ICH in individual patients. Therefore, goals such as the desired CPP and conditions such as the relative contribution of edema, cerebral hypervolemia, and ischemia to ICH should optimally be considered in a patient-specific fashion and allow a targeted approach to therapy.
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PMID:Intracranial pressure. Monitoring and management. 782 72

Experimental models of focal cerebral ischemia have provided important data on early circulatory and biochemical changes, but typically their correspondence with metabolic and hemodynamic findings in stroke patients has been poor. To fill the gap between experimental studies at early time points and rather late clinical studies, we repeatedly measured CBF, CMRO2, oxygen extraction fraction (OEF), cerebral blood volume (CBV), and CMRglc in six cats before and up to 24 h after permanent middle cerebral artery (MCA) occlusion (MCAO), using the 15O steady state and [18F]fluorodeoxy-glucose methods and a high-resolution positron emission tomography (PET) scanner. Likewise, three sham-operated control cats were studied during the same period. Final infarct size was determined on serial histologic sections. In the areas of final glucose metabolic depression that were slightly larger than the histologic infarcts, mean CBF dropped to approximately 40% of control values immediately on arterial occlusion. If further decreased to < 20% during the course of the experiment. This progressive ischemia was most conspicuous in border zones. CMRO2 fell to a lesser degree (55%), eventually reaching approximately 25% of its control level. At early stages, OEF increased mainly in the center of ischemia. With time, areas of increased OEF moved from the center to the periphery of the MCA territory. Concurrently, progressive secondary decreases in OEF in conjunction with further reductions of CBF and CMRO2 indicated the development of central necrosis. The findings are highly suggestive of a dynamic penumbra. In five cats with complete MCA infarcts, CBF decreased and OEF increased in the contralateral hemisphere after 24 h, suggesting whole-brain damage. This effect may be explained by the widespread brain edema found histologically in addition to the nonspecific CBF reductions and OEF elevations observed also in the sham-operated controls after 1 day in the experimental condition. In one cat, cortical OEF increased only transiently. Normal CMRO2 and CMRglc were eventually restored, and the final infarct was small. This study demonstrates that acute regional pathophysiologic changes can be repeatedly assessed by multivariate PET in cats. Viable tissue can be detected up to several hours after MCA occlusion, and the transition of misery-perfused regions into necrosis or preserved tissue can be followed over time. The present results support the concept of a dynamic penumbra, in which for up to 24 h tissue damage spreads progressively from the center to the periphery of ischemia. Sequential high-resolution PET provides insight into the dynamics of regional pathophysiology and may thus further the development of rational therapeutic strategies.
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PMID:Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats. 792 54

Temporary and/or permanent occlusion of carotid artery is one of the most important strategy in the surgical treatment for cervical vascular and paraclinoid lesions. Cerebral ischemia produced by this procedure should be preoperatively grasped for the safety of the surgeries. Matas test has been widely applied to estimate the collateral blood flow at the main artery occlusion by observing only clinical features. In this study, we measured CBF and common carotid artery stump pressure (CCA stump P) in contrast to angiographic cross-filling in 43 carotid endarterectomy (CEA) patients to quantitatively evaluate Matas test. The patients were manually occluded the CCA on the affected side and clinically observed for at least 10 minutes. CCA stump P and cross-filling were evaluated in all patients and CBF measurements were carried out in the patients who clinically tolerated Matas test. CBF studies were performed by single photon emission CT with Xe-133 inhalation method and CBF values were obtained in the middle cerebral artery territory before and during Matas test. CCA stump P was measured during carotid angiography by manual occlusion of the proximal site of the CCA. Cross-filling was evaluated with the contralateral carotid angiography during the manual occlusion of the affected CCA. CBF changes in Matas test were classified into the following four patterns; bilateral mild decreases in CBF, unilateral severe decrease in CBF, unilateral mild decrease in CBF and no decrease in CBF. The frequency of bilateral mild decreases in CBF, unilateral severe decrease in CBF, unilateral mild decrease in CBF and no decrease in CBF were 8, 10, 14, 7 of 43 patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Evaluation of Matas test by CBF studies, angiographic cross-filling and stump pressure in CEA patients]. 794 20

We investigated the immediate effect of tris (hydroxymethyl) aminomethane (THAM) and NaHCO3 on focal cerebral ischemia produced by occlusion of the left middle cerebral artery (MCA) in cats. The animals were divided into three groups. In the control group, physiological saline was infused continuously. The THAM and NaHCO3 groups received continuous administration of 0.3 mol THAM and 7% NaHCO3, respectively, to normalize arterial pH. Local CBF measured in the marginal and suprasylvian gyri decreased less than 30 ml/100 g/min after the MCA occlusion and there were no significant differences among the three groups. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.21 to 6.86 in the control group. However, extracellular pH did not show significant changes in the THAM and NaHCO3 groups. Intracellular pH of the infarct area decreased from 7.23 to 6.13 in the control group within 6 hours after occlusion. THAM had a tendency to normalize intracellular pH compared with that in the control and NaHCO3 groups. THAM significantly (p < 0.05) decreased water content of the gray matter in the marginal gyrus at 6 hours after occlusion and the infarct size compared with those in the control and NaHCO3 groups. Therefore, normalization of systemic and perifocal acidosis with THAM is effective for reducing cortical edema and infarct size in the early stage of focal cerebral ischemia probably due to the improvement of intracellular acidosis.
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PMID:The effect of alkalizing agents on experimental focal cerebral ischemia. 797 80

We addressed the mechanism for reduced pial vascular reactivity to muscarinic stimulation by evaluating pial vessel responses to receptor-dependent [10(-5) M acetylcholine (ACh)] and independent (10(-5) M A-23187) agonists and the endothelium-independent nitric oxide (NO) donor [10(-5) M nitroprusside (NP)]. Cerebral blood flow (CBF, microspheres) and pial arteriolar diameters (intravital microscopy) were measured in halothane-anesthetized cats. Cats (n = 13) were treated with 12 min of near-complete global cerebral ischemia, whereas control animals (n = 9) were identically instrumented but were not submitted to ischemia. Postischemic hypoperfusion was evident in most animals at 60 min of reperfusion, accompanied by attenuated pial arterial dilation to topical ACh (baseline dilation 23 +/- 4% vs. postischemia 11 +/- 3%) and A-23187 (16 +/- 4 vs. 0 +/- 3% dilation). Dilation to NP was unaffected. CBF response to intravenous administration of the muscarinic receptor agonist oxotremorine was also decreased throughout the forebrain (162 +/- 12 vs. 116 +/- 6% increase in flow) in these cats. These data suggest that endothelium-dependent vasodilation with topical muscarinic agonists is impaired during hypoperfusion, but vascular smooth muscle responsivity to NO remains intact. We conclude that the defect in the signal transduction pathway is not limited to the receptor and may involve an abnormality with NO synthesis or its destruction within endothelium.
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PMID:Effect of postischemic hypoperfusion on vasodilatory mechanisms in cats. 797 32


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