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

Contralateral cerebellar diaschisis, hypometabolism in the cerebellum contralateral to a cortical lesion, is a well described phenomenon in patients with stroke and brain tumor. However, few reports exist of patients with cerebellar lesions with the finding of contralateral cortical hypometabolism. The authors present a case of a patient with a right cerebellar astrocytoma after surgical resection and radiation therapy in which fluorine-18 fluorodeoxyglucose positron emission tomographic imaging, performed to rule out recurrent tumor, revealed global hypometabolism in the left cerebral cortex. The concept of contralateral cortical diaschisis and possible mechanisms and clinical implications are reviewed.
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PMID:Contralateral cortical diaschisis in a patient with cerebellar astrocytoma after radiation therapy. 1083 90

Iron that is not bound to storage proteins can catalyse the generation of toxic hydroxyl radicals. Iron can be released from brain storage proteins by hypoxic conditions, such as those that accompany stroke, and the situation can be compounded by iron released from hemoglobin in extravasated blood cells. Despite the neurotoxicity of iron, there is little quantitative data concerning the spatio-temporal extent of its toxicity in vivo. The present study measures the effects of a pathologically relevant concentration of iron (1.0 mM) on neuronal death and on ferritin expression in vivo. Injection of iron (1 microl ferric ammonium citrate) into rat parietal cortex resulted in 7.9-fold more ferritin-labeled cells than did control injections of ammonium citrate at 1 day post-injection. This elevated expression continued for at least 1 week. One day after injection, the mean number of Fluoro-Jade-labeled degenerating neurons in 100 microm sections passing through the center of ferric ammonium citrate injection sites was 664+/-64. This value was 4.5-fold higher than at ammonium citrate injection sites, and this difference increased to 56-fold by day three. By 5 days post-injection, few dying neurons were observed at the control sites, but neurodegeneration continued beyond a week at the iron-injected sites. Thus, iron released during a brief episode of hypoxia-ischemia or during a stroke may be neurotoxic for a protracted period. Therefore, our findings indicate that it may be beneficial to target iron-induced peroxidation throughout the first few weeks following an intracerebral hemorrhage or an hypoxic-ischemic episode.
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PMID:Quantitative analysis of cell death and ferritin expression in response to cortical iron: implications for hypoxia-ischemia and stroke. 1143 Sep 1

The dopamine-releasing and depleting substance amphetamine (AMPH) can make cortical neurons susceptible to damage, and the prevention of hyperthermia, seizures and stroke is thought to block these effects. Here we report a 2-day AMPH treatment paradigm which affected only interneurons in three cortical regions with average or below-average dopamine input. AMPH (six escalating doses/day ranging from 5 to 30 mg/kg for 2 days) was given at 17-18 degrees C ambient temperature (T) to adult male rats. During the 2-day AMPH treatment, peak body T stayed below 38.9 degrees C in 40% of the AMPH treated rats. In 60% of the rats, deliberate cooling suppressed (<39.5 degrees C) or minimized (<40.0 degrees C) hyperthermia. Escalation of stereotypes to seizure-like behaviors was rare and post-mortem morphological signs of stroke were absent. Neurons labeled with the anionic, neurodegeneration-marker dye Fluoro-Jade (F-J) were seen 1 day after dosing, peaked 3 days later, but were barely detectable 14 days after dosing. Only nonpyramidal neurons in layer IV of the somatosensory barrel cortex and in layer II of the piriform cortex and posterolateral cortical amygdaloid nucleus were labeled with Fluoro-Jade. Isolectin B-labeled activated microglia were only detected in their neighborhood. F-J labeled neurons were extremely rare in cortical regions rich in dopamine (e.g. cingulate cortex), and were absent in cortical regions with no dopamine (e.g. visual cortex). Parvalbumin was seen in some Fluoro-Jade-labeled neurons and parvalbumin immunostaining in local axon plexuses intensified. This AMPH paradigm affected fewer cortical regions, and caused smaller reduction in striatal tyrosine hydroxylase (TH) immunoreactivity than previous 1-day AMPH regimens generating seizures or severe (above 40 degrees C) hyperthermia. Correlation between peak or mean body T and the extent of neurodegeneration or microgliosis was below statistical significance. Astrogliosis (elevated levels of the astroglia-marker, glial fibrillary acidic protein (GFAP)) was detected in many brain regions. In the striatum and midbrain, F-J labeled neurons and activated microglia were absent, but astrogliosis, decreased TH immunolabel, and swollen TH fibers were detected. In sum, after this AMPH treatment, cortical pyramidal neurons were spared, but astrogliosis was brain-wide and some interneurons and microglia in three cortical regions with average or below-average dopamine input remained sensitive to AMPH exposure.
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PMID:Parvalbumin neuron circuits and microglia in three dopamine-poor cortical regions remain sensitive to amphetamine exposure in the absence of hyperthermia, seizure and stroke. 1246 30

Nuclear medicine imaging can play an important role in the diagnosis of stroke risk, the differential diagnosis of vascular and parenchymal cerebral abnormalities, and the understanding and management of poststroke recovery. Radionuclide brain-imaging methods can assess hemodynamic, vascular, and metabolic status before and after stroke. Several techniques, including vasodilatory stress imaging with regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT), oxygen extraction methods with positron emission tomography (PET), and spectroscopic imaging with magnetic resonance spectroscopic imaging, offer ways to distinguish vascular from parenchymal dysfunction and to determine whether any observed abnormalities in cerebral blood flow are primary or secondary disease manifestations. The value of radionuclide imaging in assessing the efficacy of several interventional surgical procedures is presented. Data from several imaging modalities bearing on the controversial issue of luxury perfusion and reperfusion injury are analyzed, including some of the discrepancies between animal and human clinical data. Imaging evidence for white matter disease and microangiopathy is analyzed, including a quantitative rCBF pattern analysis that distinguishes between typical Alzheimer's disease and microangiopathy by using multivariate analysis of variance curve profile analysis, which shows results of significant differences in the circumferential cortical blood flow profiles at P =.01. Microangiopathy showed rCBF reduction in the frontal and frontotemporal regions as compared with the more typical reduction in posterior temporal-parietal rCBF diminution characteristic of Alzheimer's disease. Several functional neuroimaging approaches to the study of cerebral poststroke reorganization are analyzed in the context of 2 major models of recovery: the resolution of diaschisis and reorganization in spared brain. Research on these issues is presented with SPECT, PET, magnetic resonance imaging, and magnetic resonance spectroscopy. Data show how standard structural magnetic resonance imaging, (99m)Tc hexamethylpropylene amine oxime SPECT, PET imaging, and magnetic resonance spectroscopy can be used to identify the extent of permanent damage versus penumbral and remote effects of a stroke. The results of the analysis of the pure-diaschisis model show a high correlation between the rCBF brain SPECT defect volume in the cortex and the magnetic resonance spectroscopic imaging (MRSI) change in the white matter. There is a statistically significant positive correlation between the 2 (P <.01; r(2) = 0.94). The increased creatine/N-acetyl aspartate and reduced rCBF are proposed to be due to an increase in the white matter creatine component due to diaschisis and the repair mechanisms associated with increased astrocytosis, in addition to a reduction of N-acetyl aspartate in diaschitic white matter. Xenon-133 dynamic SPECT is shown to be a quantitative and sensitive measure of cerebrovascular status and hemodynamic constraints in both spared and affected brain, providing evidence for reorganization and cerebral plasticity. Fluorine-18 PET and (31)P spectroscopic imaging data show reorganizational changes in the contralesional hemisphere after stroke. The phosphocreatine-adenosine triphosphate ratio in the contralesional hemisphere was 38% +/- 17% higher than in the ipsilateral hemisphere. The phosphocreatine-adenosine triphosphate ratio was highly correlated (r = 0.88, P <.05) with increasing (18)F-fluorodeoxyglucose uptake. These results showed that there is a parallel change in glucose metabolism and high-energy phosphate metabolism associated with poststroke recovery that is proposed to be due to cerebral reorganization in the contralateral premotor cortex. The value of these results on rehabilitation strategy, including possible criteria for the use of facilitatory versus compensatory approaches, is analyzed.
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PMID:Neuroimaging in cerebrovascular disorders: measurement of cerebral physiology after stroke and assessment of stroke recovery. 1260 57

(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct.
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PMID:Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats. 1281 59

We have previously demonstrated that neuregulin-1 (NRG-1) is upregulated and is neuroprotective in ischemic brain injury, however the expression and localization of its receptors during ischemia has not been investigated. Therefore, we used a rat middle cerebral artery occlusion (MCAO) model to examine the distribution of erbB receptors following ischemic stroke. Like neuregulin-1, we observed a dramatic induction of erbB4 in the peri-infarct regions of the ipsilateral cortex 24 h following MCAO. Using Fluoro-Jade B (FJB) staining as a marker of neurodegeneration, erbB4 was upregulated in FJB-positive cells, suggesting that erbB receptors are induced in injured neurons. The increase in erbB receptors was seen in neurons and a subpopulation of macrophages/microglia. There was no erbB co-localization with GFAP-positive astrocytes. These results demonstrate that erbB receptors are upregulated in neurons and macrophages/microglia following ischemic stroke and may be involved in neuroprotection and repair.
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PMID:Upregulation of erbB receptors in rat brain after middle cerebral arterial occlusion. 1569 57

Animal models of cerebral infarction are crucial to understanding the mechanisms of neuronal survival following ischemic brain injury and to the development of therapeutic interventions for victims of all types of stroke. Rodents have been used extensively in such research. One rodent model of stroke utilizes either permanent or temporary occlusion of the middle cerebral artery (MCAO) to produce ischemia. Since the development of an endovascular method for this was published in 1989, MCAO has been applied commonly to the rat, and often paired with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining for stroke volume measurement. Meanwhile, advances in the ability to genetically alter mice have allowed exciting lines of research into ischemia. Because of technical demands and issues with survival, relatively few laboratories have investigated the MCAO method in the mouse. Our present work utilizes a mouse middle cerebral occlusion (MCAO) model of embolic stroke to study neuronal degeneration following temporary focal cerebral ischemia. C57Bl/6J mice were used to examine the exact effects of MCAO using Fluoro-Jade, a marker of neurodegeneration that allows observation of specific brain regions and cells destined to die. A time course of escalating neuronal degeneration from 10 min to 7 days following MCAO was established. Technical aspects of this popular method for transient focal ischemia as it applies to the mouse are discussed.
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PMID:Temporary focal ischemia in the mouse: technical aspects and patterns of Fluoro-Jade evident neurodegeneration. 1582 50

We have previously shown that neuregulin-1 (NRG-1) protects neurons from ischemic brain injury if administered before focal stroke. Here, we examined the therapeutic window and functional recovery after NRG-1 treatment in rats subjected to 90 mins of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion. Neuregulin-1 (2.5 microg/kg [corrected] bolus, 1.25 microg/kg/min [corrected] infusion) reduced infarct volume by 89.2%+/-41.9% (mean+/-s.d.; n=8; P<0.01) if administered immediately after the onset of reperfusion. Neuroprotection was also evident if NRG-1 was administered 4 h (66.4%+/-52.6%; n=7; P<0.01) and 12 h (57.0%+/-20.8%; n=8; P<0.01) after reperfusion. Neuregulin-1 administration also resulted in a significant improvement of functional neurologic outcome compared with vehicle-treated animals (32.1%+/-5.7%; n=9; P<0.01). The neuroprotective effect of the single administration of NRG-1 was seen as long as 2 weeks after treatment. Neurons labeled with the neurodegeneration marker dye Fluoro-JadeB were observed after MCAO in the cortex, but the numbers were significantly reduced after NRG-1 treatment. These results indicate that NRG-1 is a potent neuroprotective compound with an extended therapeutic window that has practical therapeutic potential in treating individuals after ischemic brain injury.
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PMID:Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke. 1613 57

Stroke is a major cause of epilepsy, but the molecular mechanisms underlying post-stroke epileptogenesis are unknown. The expression of cystatin C, a cysteine protease inhibitor, is increased in the hippocampus during status epilepticus (SE)-induced epileptogenesis, and regulates both cell death and birth. To test the hypothesis that increased cystatin C expression represents a common molecular alteration induced by epileptogenic brain insults, we investigated the time course, cellular localization, and association of cystatin C expression with neuronal damage during post-stroke epileptogenesis. Stroke was induced with photothrombosis, which leads to epilepsy in approximately 20-30% of rats. Cystatin C expression was increased in the CA1 area of the hippocampus 4 days after photothrombosis, when the diameter of the lesion was the largest. Double-labeling and confocal analysis indicated that cystatin C was expressed in astrocytes and microglia. Unlike after SE, cystatin C expression did not change in the dentate gyrus. Also, increased cystatin C expression was not associated with neurodegeneration, which was demonstrated as an absence of Fluoro Jade B-positive cells in adjacent sections. The present study provides evidence that cystatin C may be involved in cellular alterations that occur after an epileptogenic insult, not only after SE but also after photothrombotic stroke.
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PMID:Cystatin C expression is increased in the hippocampus following photothrombotic stroke in rat. 1630 30

Knowledge about the molecular mechanisms of neuronal survival following ischemia is crucial to the development of therapeutic interventions for victims of stroke. Previous research in our laboratory has implicated nuclear factor-kappaB (NF-kappaB) as contributing to neuronal survival in response to toxic or ischemic brain insult, with in vivo models having focused on the rat. To take advantage of genetic alterations available in the mouse, we utilized a murine transient endovascular middle cerebral artery occlusion (MCAO) model to examine the influence of NF-kappaB on neuronal survival. When brains were immunostained for the nuclear localization sequence (NLS) of the p50 subunit of NF-kappaB, a unilateral increase in immunoreactivity was seen, especially in pyramidal cell layers of the ipsilateral (stroked) hippocampus. When transgenic mice lacking p50 were compared with non-transgenic counterparts using Fluoro-Jade, a marker for neurodegeneration, both the hippocampus and striatum showed enhanced neurodegeneration at various survival times after 1 h of MCAO. In the hippocampus specifically, there was an eightfold increase in Fluoro-jade staining in the p50 knockout group vs. the non-transgenic group. Sections double stained for Fluoro-Jade and NF-kappaB activity (using a mouse engineered with a NF-kappaB responsive promoter driving a LacZ gene to produce beta galactosidase) demonstrated neuronal degeneration only in regions sparsely showing NF-kappaB activity, and those demonstrating NF-kappaB activity failed to degenerate. These data provide evidence that NF-kappaB participates in survival signaling following temporary focal ischemia, and thus may represent an attractive target for pharmacologic activation in the treatment of stroke.
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PMID:NF-kappaB protects neurons from ischemic injury after middle cerebral artery occlusion in mice. 1663 May 92


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