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

Cerebral ischemia is followed by a local inflammatory response that is thought to participate in the extension of the tissue damage occurring in the postischemic period. However, the mechanisms whereby the inflammation contributes to the progression of the damage have not been fully elucidated. In models of inflammation, expression of the inducible isoform of nitric oxide synthase (iNOS) is responsible for cytotoxicity through the production of large amounts of nitric oxide (NO). In this study, therefore, we sought to establish whether iNOS is expressed in the ischemic brain. Rats were killed 6 h to 7 days after occlusion of the middle cerebral artery. iNOS expression in the ischemic area was determined by reverse-transcription polymerase chain reaction. Porphobilinogen deaminase mRNA was detected in the same sample and used for normalization. In the ischemic brain, there was expression of iNOS mRNA that began at 12 h, peaked at 48 h, and returned to baseline at 7 days (n = 3/time point). iNOS mRNA expression paralleled the time course of induction of iNOS catalytic activity, determined by the citrulline assay (17.4 +/- 4.4 pmol citrulline/micrograms protein/min at 48 h; mean +/- SD; n = 5 per time point). iNOS immunoreactivity was seen in neutrophils at 48-96 h after ischemia. The data provide molecular, biochemical, and immunocytochemical evidence of iNOS induction following focal cerebral ischemia. These findings, in concert with our recent demonstration that inhibition of iNOS reduces infarct volume in the same stroke model, indicate that NO production may play an important pathogenic role in the progression of the tissue damage that follows cerebral ischemia.
J Cereb Blood Flow Metab 1995 May
PMID:Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. 753 97

The therapeutic time window for N-methyl-D-aspartate (NMDA) antagonists, non-NMDA antagonists, and glutamate release inhibitors in focal models of ischemia appears to be about 1-2 h. In contrast, a free radical spin trap was found to have an improved therapeutic window. We compared the therapeutic time windows of the NMDA antagonist dizolcilpine maleate (MK-801), the glutamate release inhibitor lamotrigine, and the free radical spin trap n-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) against striatal lesions produced by the mitochondrial toxin malonate, which produces histotoxic hypoxia. Lamotrigine exerted neuroprotective effects when administered at 1 h before malonate injections. MK-801 protected at 1 h before and 1 h after malonate injections, whereas S-PBN showed efficacy when administered up to 6 h after malonate injections. Striatal injections of malonate produced a rapid increase in lactate production and early changes in diffusion-weighted imaging as assessed by magnetic resonance imaging. Therefore, the time course to evolve a lesion in our model of histotoxic hypoxia is comparable with that of other models of focal ischemia. These findings provide direct evidence that a free radical spin trap has an improved therapeutic window compared to an NMDA antagonist and a glutamate release inhibitor. This could be a therapeutic advantage in the treatment of clinical stroke patients.
J Cereb Blood Flow Metab 1995 Nov
PMID:Improved therapeutic window for treatment of histotoxic hypoxia with a free radical spin trap. 759 55

The first 2 h of middle cerebral artery occlusion (MCAO) are likely critical in determining the final outcome in ischemic stroke. To study this early postischemic period, male Wistar rats (n = 161) were subjected to right MCAO with closely spaced step variations in both duration of MCAO and blood pressure (BP), using the intraluminal suture technique. Quantitative neuropathology was performed at 25 coronal planes of the brain after 1-week survival. Atrophy was measured as the difference between the two hemispheres and was added to cortical and striatal necrosis to obtain total tissue loss. Damage consistently increased monotonically with increasing duration of occlusion only when infarct size was expressed as percentage of the contralateral hemisphere, but not when expressed as mm3, because of variable tissue size. The results showed that already at 1 week, the quantity of tissue loss due to resorption and transsynaptic effects approached the quantity of geographically traceable necrosis in cortex and striatum. Minimum brain damage (5%) occurred after 60 min at a BP of 80 mm Hg, with almost no cortical necrosis. Damage was extremely sensitive to hypotension and MCAO duration. At a BP of 40 mm Hg, 60 min of MCAO produced 25% damage, accelerating every 20 min during the 2-h period studied. At BP 80 mm Hg, 120 min of MCAO produced the same damage as only 80 min of MCAO at BP 60 mm Hg. At 60-, 80-, 100-, and 120-min duration of MCAO, infarct size was significantly reduced with increasing BP.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1995 Nov
PMID:Graded hypotension and MCA occlusion duration: effect in transient focal ischemia. 759 59

Irreversible anoxic injury is dependent on extracellular Ca2+ in mammalian CNS white matter, with a large portion of the pathologic Ca2+ influx occurring through reverse Na(+)-Ca2+ exchange, stimulated by increased intracellular [Na+]. This Na+ leak likely occurs via incompletely inactivated voltage-gated Na+ channels. This study reports that clinically used antiarrhythmic compounds, likely by virtue of their Na+ channel-blocking properties, significantly protect CNS white matter from anoxia at concentrations that cause little suppression of the preanoxic response. Rat optic nerves were pretreated with various agents for 60 min, then subjected to 60 min of anoxia in vitro. Functional recovery was measured electrophysiologically as the area under the compound action potential (CAP). Without drug, the CAP areas recovered to a mean of 32 +/- 12% of control after 1 h of reoxygenation. Recoveries using prajmaline 10 microM were 82 +/- 15% (p < 0.0001), and using tocainide 1 mM, 78 +/- 8% (p < 0.0001), with little suppression (< or = 10%) of the preanoxic response. Ajmaline (10-100 microM), disopyramide (10-300 microM) and bupivacaine (10-100 microM) were somewhat less effective, whereas verapamil produced 52 +/- 11% recovery before reduction of the preanoxic CAP was observed at 30 microM. Procainamide (100-300 microM) was ineffective. These results suggest that Na+ channel blockers, including commonly used antiarrhythmic agents, may be effective in protecting central white matter, which is a target for anoxic/ischemic injury in diseases such as stroke and spinal cord injury.
J Cereb Blood Flow Metab 1995 May
PMID:Protective effects of antiarrhythmic agents against anoxic injury in CNS white matter. 771

In this study we evaluated the effect of the competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CGP 40116) on both early (2 days) and late (28 days) ischemic brain damage in a rodent model of focal cerebral ischemia by means of magnetic resonance imaging (MRI) and conventional histology. Immediately after occlusion of the left middle cerebral artery (MCA), rats received either CGP 40116 (20 mg/kg i.p.) or isotonic saline. Two MRI scans were performed in each animal 2 and 28 days after MCA occlusion. After the second scan, rats were perfusion fixed for histological evaluation. The volume of lesioned brain tissue as determined by MRI or histology was calculated from the damaged area in single sections and the distance between them. CGP 40116 reduced acute infarct volume as measured by MRI 2 days after MCA occlusion by 44% (p < 0.05, analysis of variance). After 28 days the lesion detected by MRI was still significantly smaller in the drug-treated animals. This finding was confirmed by the histological analysis showing a 64% reduction in the volume of brain atrophy in the CGP 40116 group (p < 0.05, analysis of variance). There was a good correlation between the MRI data and the results of the histological evaluation (r = 0.9). Our results indicate that (a) the competitive NMDA antagonist CGP 40116 permanently protects brain tissue from the consequences of cerebral ischemia in a rat model for human stroke and (b) early and late pathological changes can be accurately measured by MRI.
J Cereb Blood Flow Metab 1995 Jul
PMID:The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats. 779 Apr 8

Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.
J Cereb Blood Flow Metab 1995 Jul
PMID:Basic fibroblast growth factor protects against excitotoxicity and chemical hypoxia in both neonatal and adult rats. 779 Apr 10

N-Acetyl-aspartate (NAA) is almost exclusively localized in neurons in the mature brain and might be used as a neuronal marker. It has been reported that the NAA content in human brain is decreased in neurodegenerative diseases and in stroke. Since the NAA content can be determined by nuclear magnetic resonance techniques, it has potential as a diagnostic and prognostic marker. The objective of this study was to examine the change of NAA content and related substances following cerebral ischemia and compare the results to the damage of the tissue. We used rats to study the changes of NAA, N-acetyl-aspartyl-glutamate (NAAG), glutamate, and aspartate contents over a time course of 24 h in brain regions affected by either permanent middle cerebral artery occlusion (focal ischemia) or decapitation (global ischemia). The decreases of NAA and NAAG contents following global brain ischemia were linear over time but significant only after 4 and 2 h, respectively. After 24 h, the levels of NAA and NAAG were 24 and 44% of control values, respectively. The concentration of glutamate did not change, whereas the aspartate content increased at a rate comparable with the rate of decrease of NAA content. This is consistent with NAA being preferentially degraded by the enzyme amidohydrolase II in global ischemia. In focal ischemia, there was a rapid decline of NAA within the first 8 h of ischemia followed by a slower rate of reduction. The reductions of NAA and NAAG contents in focal ischemia were significant after 4 and 24 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1995 Jul
PMID:Changes in N-acetyl-aspartate content during focal and global brain ischemia of the rat. 779 Apr 13

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.
J Cereb Blood Flow Metab 1995 Jul
PMID:Postischemic cerebral blood flow recovery in the female: effect of 17 beta-estradiol. 779 Apr 16

Recent developments in diffusion-weighted imaging (DWI) have enabled the pathological changes that occur during cerebral ischaemia to be studied. The present studies utilised DWI to investigate the development of early ischaemic changes following permanent middle cerebral artery (MCA) occlusion in the rat, which represents a model of stroke. An increased DWI signal was seen in the region of the occluded MCA and this was detectable as early as 1 h postocclusion. DWI images were obtained at nine stereotactic levels throughout the brain, providing a quantifiable measure of the volume of increased signal intensity in each animal. At 1 h post-MCA occlusion the hyperintense areas were seen in the frontoparietal cortex and lateral caudate nucleus; these areas represent the core of the infarct and no protection is seen with any compounds in these areas. There was a progressive increase in the area of hyperintensity up to 4 h post-MCA occlusion, and at this time point the hyper-intensity was seen in the dorsolateral cortex and caudate nucleus. At 4 h post-MCA occlusion there was a significant correlation between the volume of hemispheric and cortical ischaemic damage measured using DWI and histology. Thus, it appears that the increased DWI signal seen during the early time points after MCA occlusion was demarcating tissue that was destined for infarction. The area beyond the hyperintense region at 1 h represents the so-called "penumbral" region, because with increasing time (post-MCA occlusion) this area became incorporated into the infarct. There was also a slight increase in infarct size between 4 and 24 h, when assessed using DWI or histology, although two groups of animals were being compared, as opposed to the time-course study, in which just one group of animals was used. At 24 h post-MCA occlusion there was a good correlation between DWI, histology, and conventional T2 weighted imaging. There was no further increase in size of the infarct between 24 h and 7 days as assessed using histology and T2-weighted imaging. DWI could not be used to quantify infarct volume at 7 days because there was no uniform signal in the damaged area. At 7 days the area of infarction actually appeared to be darker in the diffusion-weighted images. The hyperintensity seen in diffusion-weighted images appears to decrease some time between 24 h and 7 days.(ABSTRACT TRUNCATED AT 400 WORDS)
J Cereb Blood Flow Metab 1995 Jan
PMID:A comparison of the early development of ischaemic damage following permanent middle cerebral artery occlusion in rats as assessed using magnetic resonance imaging and histology. 779 26

Anatomical and physiological investigations indicate two major distinct functional streams within the extrastriate visual cortex of the macaque monkey, and behavioral observations suggest that the ventral (occipitotemporal) pathway is the cornerstone for object recognition whereas the dorsal (occipitoparietal) pathway is primarily involved in visuospatial perception and visuomotor performance. In the context of this dichotomy we conducted a psychophysical and neuropsychological study of visual perceptual abilities in two stroke patients, each with lesions involving several extrastriate areas. Magnetic resonance imaging demonstrated bilateral lesions; in one patient (E.W.) the lesion involves the ventral medial portions of the occipital and temporal lobes, and in the other (A.F.) the lesion involves dorsally the occipital-parietal area, including the region of the temporal-parietal-occipital junction. E.W. suffers from achromatopsia of central origin, prosopagnosia, visual agnosia, and alexia without agraphia. His depth and motion perception, including recognition of moving objects, are normal. He has superior visual field loss bilaterally, and slightly impaired acuity, and complains that the world appears in a deep twilight even on a sunny day. In contrast, A.F. shows specific deficits of stereopsis, spatial localization, and several aspects of motion perception. He is also impaired at recognizing objects presented from unconventional views, but recognition of prototypical views of objects, and color and form discrimination are normal, as is his ability to recognize faces. The anatomical characteristics of the lesions of these two patients permit a direct experimental comparison of the effects of lesions confined to the parietal or temporal pathways. E.W.'s and A.F.'s performance on the psychophysical and neuropsychological tasks discussed here supports the functional distinction between a dorsal and a ventral extrastriate system but additionally suggests the existence of a pathway involved in identification-from-motion that is separate from both the dorsal early motion/spatial analysis pathway and the ventral color/static-form pathway.
Cereb Cortex
PMID:Functional segregation of color and motion processing in the human visual cortex: clinical evidence. 783 56


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