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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent investigations have demonstrated internucleosomal DNA fragmentation in ischemic neuronal tissue. This type of fragmentation is characteristic of programmed cell death or apoptosis and suggests that neuronal death in stroke may be more complex than simple necrotic death. The present experiments provide a detailed examination of the regional localization and time course for apoptotic DNA fragmentation in the cerebral cortex following focal cerebral ischemia. Spontaneously hypertensive rats were subjected to permanent right middle cerebral artery occlusion and the cerebral cortices were examined for evidence of DNA fragmentation using electrophoretic, flow cytometric, and histological approaches. An electrophoretic examination of cortical DNA at 24 h after the occlusion indicated that the majority of nucleosomal ladders were in the transition zone or penumbra and the core of the infarction, with no fragmentation apparent in the contralateral normal cortex. A flow cytometric analysis of DNA fragmentation in intact cells revealed a similar pattern, with increased fragmentation observed in ischemic cortex vs. the contralateral cortex. Saggital sections taken 1.5 mm lateral to midline were collected from animals at 1, 4, and 24 h after the infarction and DNA fragmentation was examined histologically by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) staining. Quantitative analysis of these sections indicated that DNA fragmentation can be observed in the anterior and central area of the infarctions as soon as 1 h after the occlusion and that the extent and magnitude of the fragmentation increases at 4 and 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apoptotic DNA fragmentation in the rat cerebral cortex induced by permanent middle cerebral artery occlusion. 749 49

There is a great deal of evidence that an ischaemic penumbra exists in animals and humans after the occurrence of focal brain ischaemia (Hossmann, 1994). The concept of the penumbra leads to the idea of a therapeutic time window. Because, if the region of irreversible injury (infarction) after focal ischaemia evolves in time and space, then the possibility of therapy to interfere becomes a tenable hypothesis. All of the acute stroke therapies given after onset have their basis from this hypothesis of a therapeutic time window (Fisher, 1995). As previously alluded to, a more apt term might be a window-shade, because this metaphor suggests a more dynamic event. The time and location of potentially salvageable ischaemic brain tissue after ischaemic stroke is a moving target and many unanswered questions remain. The data from animal stroke models support 2-3 hours as the time when intervention is likely to be beneficial in rats. Non-human primate data are scarce, but the few studies available do imply that at 3-4 hours after stroke onset some ischaemic tissue remains potentially salvageable. In humans, we really do not know what the time window is and we must remember that it is likely to be highly variable among individuals. This variability relates to many factors including the status of collateral flow, patient age, coexistent metabolic abnormalities (i.e. hyperglycaemia), premorbid medications and many other confounding variables. All acute stroke intervention trials are trying to initiate therapy within 6-8 hours after onset and the earlier, presumably the better. However, this approach is based upon population averaging, since we have had no convenient and reliable mechanism to determine, if an individual patient has viable tissue when therapy can be started. The availability of an imaging modality that could distinguish the presence and extent of salvageable ischaemic tissue would greatly facilitate stroke therapy trials and ultimately the selection of patients when proven therapies are available. The new MRI techniques might afford this possibility. As we enter the exciting era of effective therapy for acute ischaemic stroke, the issues surrounding the therapeutic time window(shade) will become more critical, because it is this critical time that will define the success or failure of our interventions. Therefore it is incumbent upon basic stroke researchers and clinicians to continue to define the ischaemic penumbra and to develop readily applicable mechanisms to identify and treat this moving target.
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PMID:The penumbra, therapeutic time window and acute ischaemic stroke. 749 21

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred. Neuropathological investigations demonstrate a reproducible damaged area surrounded by a thin peripheral area showing neuronal apoptotic phenomena. The method represents a reproducible model of focal cerebral ischemia with neuropathological aspects superimposable to those characteristic of thrombogenic stroke in man. This method could also be relevant in the study of neurotransmitters during the evolution of ischemia. Furthermore, the presence of apoptotic phenomena in the perilesional halo confirms an ischemic penumbra suggesting the significance of preclinical pharmacological trials.
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PMID:Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats. 756 38

A 64-year-old man had an ischemic stroke in the left parietotemporal cortical-subcortical areas. He developed a severe right spastic hemiparesis and dysphasia. An angiographic study showed left internal carotid artery occlusion and right internal carotid artery stenosis. A right internal endoarteriectomy was performed without any clinical improvement. After 1 year the patient was a candidate for cervical spinal cord stimulation (SCS) for the treatment of his spastic hemiparesis. An epidural electrode (Medtronic Sigma 3483) was positioned at the cervical level, mediodorsal to the cord. Clinical and neurophysiological studies (surface polyelectromyography, PEMG, for evaluation of brain motor control) were performed before and after 7 days of SCS (0.2 ms, 80 c/s, intensity for paresthesiae, continuous mode). A transcranial Doppler (TCD) study of both middle cerebral arteries (MCA) at rest and during SCS was performed on two occasions. SCS was followed by improvement of voluntary movement, decrease of spasticity and better endurance. The clinical findings were confirmed by the PEMG recordings. TCD examination showed an increase of flow velocities on both the right MCA (+43%) and the left MCA (+130%) during SCS. Such a TCD pattern, suggesting an increase of cerebral blood flow (CBF) during SCS, was reproducible. This case confirms efficacy of SCS in the treatment of ischemic hemiparesis and the increase of CBF following cervical SCS in man. The marked increase of CBF, particularly evident on the ischemic side, may play a role in mediating the improvement of motor control in our patient together with a possible arousal of the so-called 'sleeping neurons' of the penumbra zone.
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PMID:Increase of cerebral blood flow and improvement of brain motor control following spinal cord stimulation in ischemic spastic hemiparesis. 763 Oct 53

Patients with acute stroke often present with high blood pressure (BP) on hospital admission. Because hypertension is a risk factor for stroke, and because severe BP elevation may increase oedema and the risk of haemorrhage, acute antihypertensive therapy might seem reasonable. On the other hand, the increase in BP in the acute stage might be considered a beneficial pathophysiological response maintaining the perfusion pressure to the ischaemic area and, in particular, the surrounding penumbra. As illustrated in the case presented here, lowering the BP in the early stage may be associated with progression of neurological deficits, very likely due to a reduction of perfusion to the penumbra thus enlarging the infarct.
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PMID:[Reducing hypertension may worsen symptoms of acute apoplexy]. 765 84

Stroke-in-progression, SIP, occurs in about 30% of patients with acute stroke and negatively affects the prognosis and mortality. The underlying caused are thought to be clot propagation, cerebral haemorrhage or oedema. In some cases these rather obvious mechanisms cannot be demonstrated, and other variables such as a decrease in blood pressure must be considered as major factors. In this paper the basic haemodynamic mechanisms of cerebral blood flow and the relevant pathophysiology of focal cerebral infarcts are described with emphasis on the penumbra. In addition, available clinical studies are reviewed and current treatment discussed. Our main conclusion is that to assure sufficient collateral flow a high perfusion pressure must be maintained, and we advocate withholding antihypertensive therapy during the acute phase of focal cerebral ischaemia.
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PMID:[Apoplexy with rapidly deteriorating symptoms--"stroke in progression". Hemodynamic and clinical aspects]. 765 6

Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PBN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PBN was given 1 hr after recirculation. Neocortical focal and perifocal ("penumbra") areas were sampled for analyses of phosphocreatine (PCr), creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion of glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PBN on mitochondria cannot be excluded, the results suggest that PBN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.
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PMID:N-tert-butyl-alpha-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. 776 48

Events associated with an evolving cerebral infarction were studied using multiple magnetic resonance imaging (MRI) techniques at 4.7 T in a rat model of middle cerebral artery occlusion. High resolution perfusion images revealed a core of absent perfusion surrounded by a zone of slow, but measurable perfusion. Only the core of severest perfusion deficit demonstrated restricted water diffusion as early as 1 hr, consistent with "cytotoxic" cellular edema in the most vulnerable region. Within 24 hours, the area of restricted diffusion encompassed the entire region destined to become infarcted. In spin-echo images, hypointensity, likely reflecting deoxygenated hemoglobin, was visible in the ischemic hemisphere. Edema accumulated over 72 hr primarily in the surrounding slowly perfused rim, consistent with the concept of "vasogenic" edema. These studies demonstrate that multimodal MRI can visualize events which define the ischemic penumbra--deoxygenation, maintenance of transmembrane ionic gradients, reduced flow, and delayed cell death. These experiments noninvasively visualized differential hemodynamic and biochemical processes within the core and perifocal penumbra and will allow quantitation over time of the relationship between blood flow, cytotoxicity and edema in stroke.
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PMID:The evolution of acute stroke recorded by multimodal magnetic resonance imaging. 780 56

BW619C89 [4-amino-2-(4-methyl-1-piperazinyl)-5-(2,3,5- trichlorophenyl)pyrimidine is a use-dependent blocker of voltage-dependent sodium channels that blocks veratrine-induced glutamate release in vitro. The aim of this study is to determine if BW619C89 inhibits glutamate release and is neuroprotective in cerebral ischemia produced by proximal middle cerebral artery (MCA) occlusion in rats. Infarct volume was determined at 24 hr after permanent MCA occlusion from 2,3,5-triphenyltetrazolim hydrochloride-stained sections. Pretreatment with BW619C89 (10, 20, 30 and 50 mg/kg i.v. of mesylate salt) decreased infarct volume in a dose-dependent fashion maximal at 30 mg/kg compared to saline controls. Treatment with 30 mg/kg up to 45 min after MCA occlusion also was effective. Microdialysate glutamate in rats treated with 30 mg/kg of drug before MCA occlusion was decreased in both caudate (ischemic core) and rostral cortex (penumbra) compared to controls. BW619C89 did not induce significant arterial hypotension, except when it was administered by rapid bolus administration. In this case, the hypotension was transient and did not reduce efficacy or superficial cortical blood flow. BW619C89 did not induce the 72 kD heat shock protein in cingulate gyrus or retrosplenial cortex as did MK801, suggesting that BW619C89 does not injure neurons in these regions as do N-methyl-D-aspartate antagonists. These results suggest that inhibition of glutamate release by BW619C89 may be an effective and nontoxic treatment for stroke.
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PMID:Neuroprotective effects of a use-dependent blocker of voltage-dependent sodium channels, BW619C89, in rat middle cerebral artery occlusion. 791 Feb 13

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


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