Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies in humans suggest that regions that show maximal increases in brain oxygen extraction fraction (OEF) in the hours following an ischemic episode are those most vulnerable for infarction and are often, although not always, associated with the final site of infarction. To clarify this issue, we followed the hemodynamic and metabolic characteristics of regions with an initially maximally increased OEF and compared them with the ultimately infarcted region in an experimental stroke model. Positron emission tomography (PET) was used to obtain functional images of the brain prior to and following reversible unilateral middle cerebral artery occlusion (MCAO) in 11 anesthetized baboons. To model early reperfusion, the clips were removed 6 h after occlusion. Successive measurements of regional CBF (rCBF), regional CMRO2 (rCMRO2), regional cerebral blood volume, and regional OEF (rOEF) were performed during the acute (up to 2 days) and chronic (> 15 days) stage. Late magnetic resonance imaging (MRI) scans (co-registered with PET) were obtained to identify infarction. Reversible MCAO produced an MRI-measurable infarction in 6 of 11 baboons; the others had no evidence of ischemic damage. Histological analysis confirmed the results of the MRI investigation but failed to show any evidence of cortical ischemic damage. The lesion was restricted to the head of the caudate nucleus, internal capsule, and putamen. The infarct volume obtained was 0.58 +/- 0.31 cm3. The infarcts were situated in the deep MCA territory, while the area of initially maximally increased OEF was within the cortical mantle. The mean absolute rCBF value in the infarct region of interest (ROI) was not significantly lower than in the highest-OEF ROI until 1-2 days post-MCAO. Cerebral metabolism in the deep MCA territory was always significantly lower than that of the cortical mantle; decreases in CMRO2 in the former region were evident as early as 1 h post-MCAO. In the cortical mantle, the rOEF was initially significantly higher than in the infarct-to-be zone. Subsequently, the OEF declined in both regions. The differences in the time course of changes in CMRO2 and OEF between these two regions, with the eventually infarcted area showing earlier metabolic degradation and in turn decline in OEF, presumably underlie their different final outcomes. In conclusion, following MCAO, the region that shows an early maximal increase in the OEF is both topographically and physiologically distinct from the region with final consolidated infarction if reperfusion is allowed at 6 h. This high OEF, although indicative of a threatened condition, is not an indicator of inescapable consolidated infarction and is thus a situation in which therapy could be envisaged. Whether or not it is at risk of infarction and thus constitutes one target for therapy remains to be seen.
 ...
PMID:Relationships between high oxygen extraction fraction in the acute stage and final infarction in reversible middle cerebral artery occlusion: an investigation in anesthetized baboons with positron emission tomography. 889 90

63 subjects with symptomatic obstructive carotid artery disease were investigated with transcranial Doppler ultrasonography. Their blood velocities at rest (V) in the middle and posterior cerebral artery (MCA and PCA) and in the extracranial internal carotid artery were measured and the pulsatility index (PI) and Uhem index (VMCA.PIMCA/VPCA.PIPCA) calculated. The vasomotor responses in both MCAs were also tested. The subjects were divided into groups based on the findings on physical examination and cerebral computed tomography. In the patient group with lacunar/territorial infarction we found in the stroke hemisphere: VMCA > VPCA, PIMCA = PIPCA and normal values for the Uhem index and total vasomotor reactivity. In the patient group with watershed infarction this hemisphere was characterized by: VMCA < VPCA, PIMCA < PIPCA and subnormal scores for the Uhem index and total vasomotor reactivity. Displaying features from both stroke groups, we obtained in the hemisphere of interest in patients with transient ischaemic attacks: VMCA = VPCA, PIMCA < PIPCA and normal values for the Uhem index and total vasomotor reactivity. Five patients with clinical evidence of stroke but with negative cerebral computed tomography findings had scores similar to those of the watershed group of patients. For the stroke patients, individual measurements of V, PI and total vasomotor reactivity failed to clearly identify to which stroke group a subject might belong. However, such an identification was achieved in all subjects when using the Uhem index. The Uhem index data in patients with transient ischaemic attacks suggest two subgroups with different pathogenesis underlying, the ischaemic events.
 ...
PMID:Haemodynamic classification of symptomatic obstructive carotid artery disease. 891 45

Because the pathogenesis of cerebral ischaemia in internal carotid artery dissection (ICAD) is controversial we studied the topography of cerebral infarction that results from ICAD according to pathophysiology of embolic and haemodynamic stroke. Sixty-four patients with 67 ICADs diagnosed by angiography, Doppler duplex sonography and magnetic resonance imaging (MRI) were studied prospectively during the past decade. According to current pathophysiological concepts, cortical territorial infarcts and large subcortical lenticulostriate infarcts revealed by CT or MRI were classified as embolic, while smaller infarcts in the subcortical junctional zone and infarcts in the cortical borderzone between the middle (MCA) and anterior cerebral artery were interpreted as haemodynamic infarcts. Of the 67 dissections 37 (55%) were associated with brain infarcts, of which territorial MCA infarcts of variable size accounted for 60%. These were combined with infarcts of the anterior and posterior cerebral artery in 5%; 8% of the patients had complete MCA infarction. Large lenticulostriate infarcts were present in 11%. Haemodynamic infarcts involved the subcortical junctional zone in 16% but never the anterior cortical borderzone. Although different abnormal Doppler findings indicated haemodynamically significant carotid obstruction in all symptomatic ICADs, only the characteristic high-resistance Doppler signal was significantly associated with the occurrence of brain infarction (in 66%, P < 0.01). The angiographic features of ICAD did not correlate with the incidence or with the topography of cerebral infarction. Patterns of infarction in ICAD indicate a predominantly embolic causation probably due to thrombus formation in the dissected carotid artery in the presence of severe haemodynamic obstruction, as demonstrated by Doppler sonography.
 ...
PMID:Topography of cerebral infarction associated with carotid artery dissection. 896 5

Severe stroke is an emergency and requires rapid neurological assessment and diagnosis. CT scan is the first diagnostic step with the aim of finding out the extent, localization and possible pathophysiology of ischaemia in order to direct specific diagnostic and therapeutic options. An intracranial haemorrhage must be excluded. Early CT signs, including the size of the hypodensity and brain swelling, are important prognostic markers. Extracranial and transcranial Doppler sonography are valid for primary assessment of vascular pathophysiology and haemodynamics in most cases. Cerebral angiography should be performed if acute occlusion of the basilar artery or middle cerebral artery trunk is suspected and intra-arterial thrombolysis is a potential therapy. Intravenous thrombolyis has been proven to be effective in improving outcome in severe stroke; it is safe if the exclusion criteria are strictly applied. Prevention of secondary complications of stroke include general medical treatment with control of blood pressure, infections and cardiac and respiratory function, anti-coagulation. anti-oedematous treatment and surgical decompressive therapy for cerebellar and MCA space-occupying infarcts. Monitoring in the ICU is recommended. The medical therapy of intracerebral haemorrhage consists of control of ventilation and blood pressure, seizure prevention and anti-oedema treatment. Treatment of secondary ICH due to anti-coagulation or thrombolysis consists of administration of specific antidotes and the correction of the coagulopathy. Ventricular drainage should be performed when there is marked ventricular dilatation due to obstruction or blood in the ventricles. Most patients with cerebellar haemorrhage of more than 3 cm in diameter should undergo surgery to avoid brain-stem compression and hydrocephalus. In younger patients, non-dominant hemisphere putaminal and lobar haemorrhages with lateral displacement of midline structures and extensive oedema should be evacuated if the patient's level of consciousness deteriorates rapidly, or if the elevation of ICP cannot be controlled pharmacologically, and herniation is incipient. New techniques such as stereotactic and endoscopic evacuation still need to be tested prospectively. Patient selection for surgery should be cautious considering age, clinical status and possible contraindications such as cerebral amyloid angiopathy and coagulation disorders. Stroke therapy is rapidly becoming a focus of research and major changes in diagnostic and therapeutic options can therefore be expected.
 ...
PMID:Severe stroke. 911 74

Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm2 calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.
 ...
PMID:Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat. 913 19

The wider clinical acceptance of thrombolytic therapy for ischemic stroke has focused more attention on experimental models of reversible focal ischemia. Such models enable the study of the effect of ischemia of various durations and of reperfusion on the development of infarctions. We used high-resolution positron emission tomography (PET) to assess cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) before, during, and up to 24 h after middle cerebral artery occlusion (MCAO) in cats. After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened after 30 min in five, after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30-min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of reperfusion. In those cats surviving the first day, infarct size was determined on serial histologic sections. The arterial occlusion immediately reduced CBF in the MCA territory to < 40% of control, while CMRO2 was less affected, causing an increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and 120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial OEF increase had already disappeared during the later period of ischemia in those cats that died during the reperfusion period. After 30-min MCAO, the reperfusion period was characterized by a transient reactive hyperemia and fast normalization of CBF, CMRO2, and CMRglc, and no or only small infarcts in the deep nuclei were found in histology. After 60- and 120-min MCAO, the extent of hyperperfusion was related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and cortical/subcortical infarcts of varying sizes developed. A clear difference was found in the flow/metabolic pattern between surviving and dying cats: In cats dying during the observation period, extended postischemic hyperperfusion accompanied large defects in CMRO2 and CMRglc, large infarcts developed, and intracranial pressure increased fatally. In those surviving the day after MCAO, increased OEF persisted over the ischemic episode, postischemic hyperperfusion was less severe and shorter, and the perfusional and metabolic defects as well as the final infarcts were smaller. These results stress the importance of the severity of ischemia for the further course after reperfusion and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfusion was also observed.
 ...
PMID:Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion. 914 21

Cytokines are recognized to play an important role in acute stroke. Tumor necrosis factor-alpha (TNF) is one of the pro-inflammatory cytokines and is expressed in ischemic brain. We hypothesized that TNF might play a role in the regulation of tolerance to ischemia when administered prior to the ischemic episode. We studied the effects of pretreatment of TNF administered intravenously, intraperitoneally, or intracisternally in mice that were subjected to middle cerebral artery occlusion (MCAO) 48 h later. MCAO was performed in BALB/C mice by direct cauterization of distal MCA, which resulted in pure cortical infarction. A significant reduction in infarct size was noted in mice pretreated by TNF at the dose of 0.5 microgram/mouse (p < 0.01) intracisternally. At the doses used in this study, administration of TNF by intravenous or intraperitoneal routes was not effective. Immunohistochemical analysis of brains subjected to 24 h of MCAO revealed a significant decrease in CD11b immunoreactivity after TNF pretreatment compared with control MCAO. Preconditioning with TNF affects infarct size in a time- and dose-dependent manner. TNF induces significant protection against ischemic brain injury and is likely to be involved in the signaling pathways that regulate ischemic tolerance.
 ...
PMID:TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice. 918 85

During reperfusion after ischemia, deleterious biochemical processes can be triggered that may antagonize the beneficial effects of reperfusion. Research into the understanding and treatment of reperfusion injury (RI) is an important objective in the new era of reperfusion therapy for stroke. To investigate RI, permanent and reversible unilateral middle cerebral artery/common carotid artery (MCA/CCA) occlusion (monitored by laser Doppler) of variable duration in Long-Evans (LE) and spontaneously hypertensive (SH) rats and unilateral MCA and bilateral CCA occlusion in selected LE rats was induced. In LE rats, infarct volume after 24 hours of permanent unilateral MCA/CCA occlusion was 31.1 +/- 34.6 mm3 and was only 28% of the infarct volume after 120 to 300 minutes of reversible occlusion plus 24 hours of reperfusion, indicating that 72% of the damage of ischemia/reperfusion is produced by RI. When reversible ischemia was prolonged to 480 and 1080 minutes, infarct volume was 39.6 mm3 and 16.6 mm3, respectively, being indistinguishable from the damage produced by permanent ischemia and significantly smaller than damage after 120 to 300 minutes of ischemia. Reperfusion injury was not seen in SH rats or with bilateral CCA occlusion in LE rats, in which perfusion is reduced more profoundly. Reperfusion injury was ameliorated by the protein synthesis inhibitor cycloheximide or spin-trap agent N-tert-butyl-alpha-phenylnitrone pretreatment.
 ...
PMID:Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. 934 29

To improve cerebral hypoperfusion in the ischemic type of Moyamoya disease, we have applied superficial temporal artery-middle cerebral artery (STA-MCA) double anastomoses in combination with encephalo-myo-synangiosis (EMS) for 19 hemispheres of 10 children (age from 5 to 11 years at surgery). Two branches of the STA were anastomosed to the two cortical arteries which were selected in the watershed area of the cerebral hemisphere estimated as a hypoperfusion area on the preoperative angiograms. Before surgery transient ischemic attacks (TIAs) developed from every month to every 6 months in association with hyperventilation or sobbing. No perioperative completed stroke or wound complications was observed, although single TIA developed in four patients within 1 month after surgery. Postoperative angiogram demonstrated that, not only the preoperative watershed area, but also the most of the middle cerebral artery territory was oppacified via the 2 branches of the STA in all 19 hemispheres. In a mean follow-up period of 4 years, no ischemic episode was induced by hyperventilation, and there was no mental or neurological deterioration. STA-MCA double anastomoses, to the cerebral watershed area, in combination with EMS are safe and effective even for younger children with Moyamoya disease.
 ...
PMID:Direct extracranial-intracranial bypass for children with moyamoya disease. 940 22

Neuronal death following cerebral vascular occlusion may be caused in part by the action of glutamate acting through the NMDA receptor. Here we demonstrate that gene disruption of the NR2C subunit of the NMDA receptor attenuates focal cerebral ischemic injury after permanent MCA occlusion, and that a low level of NR2C is expressed and active in the cerebral cortex. NR2C-deficient mice do not show impairment of motor coordination or motor learning. Therefore the development of drugs selectively inhibiting NR2C may prove beneficial in the treatment of stroke and traumatic brain injuries.
 ...
PMID:Attenuation of focal cerebral infarct in mice lacking NMDA receptor subunit NR2C. 951 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>