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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,3,5-Triphenyltetrazolium chloride (TTC) staining is a convenient procedure for detection of brain infarcts but no standardized procedure is available. We report here an optimized and economic procedure of staining with TTC. Rats were subjected to reversible middle cerebral artery (MCA) occlusion (2-h ischemia and 24-h reperfusion). At the end of reperfusion, brain was isolated and sliced rostro-caudally into serial 2-mm-thick slices. Sets of three serial slices from each brain were incubated for 30 min at 37 degrees C in three different concentrations of TTC-the first slice of the set in 1%, the second in 0.05% and the third in 0.1% TTC-in phosphate-buffered saline. Staining characteristics, optical density (OD) and infarct size were compared between juxtaposing cut surfaces of the slices stained with the three concentrations of TTC. After the first use, 0.05% TTC solution was stored at 4-8 degrees C and reused on the same day or on subsequent days. TTC at 0.05% concentration provided high contrast staining with clear demarcation between normal and infarct tissue. The infarct size in 0.05% TTC-stained slices correlated well with that in 0.1% TTC (r=0.92)- and 1% TTC (r=0.93)-stained preparations. 'Nonspecific' staining of corpus callosum and the anterior commissures was minimal with the method. Once-used 0.05% TTC solution could be stored at 4-8 degrees C and reused. In conclusion, staining with 0.05% TTC provided improved delineation of brain infarcts, reduced 'nonspecific' staining of white matter and the infarct size correlated well with that measured after 1% TTC staining; the method also reduces the costs to 1/20.
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PMID:An optimized triphenyltetrazolium chloride method for identification of cerebral infarcts. 1506 36

Methotrexate, an anti-rheumatic agent, has recently been reported to show an anti-inflammatory action via ecto-5'-nucleotidase- and adenosine-dependent mechanisms. Because ecto-5'-nucleotidase contributes to the production of adenosine and adenosine has a potent cardioprotective effect against ischemia/reperfusion injury, we investigated whether methotrexate or MX-68 [N-1-((2,4-diamino-6-pteridinyl) methyl)-3,4-dihydro-2H-1,4-benzothiazine-7- carbonyl]-N-2- aminoadipic acid] could reduce infarct size via adenosine-dependent mechanisms. In beagle dogs, the left anterior descending coronary artery was perfused through a bypass tube, which was occluded for 90 minutes followed by 6 hours of reperfusion. The size of infarcts was assessed by TTC staining. MX-68 reduced infarct size compared with that in untreated dogs (13.7 +/- 1.9 versus 38.6 +/- 5.3%, P < 0.01). This effect was completely blunted by either the adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) (45.0 +/- 4.6% and 46.8 +/- 5.8% in the 8-SPT and MX-68 + 8-SPT groups, respectively) or by the ecto-5'-nucleotidase inhibitoralpha,beta-methylenadenosine 5'-diphosphate (AMP-CP) (44.0 +/- 4.5% and 46.7 +/- 5.8% in the AMP-CP and MX-68 + AMP-CP groups, respectively). Methotrexate also reduced infarct size to a level comparable with that in the MX-68 group, and its effect was also blunted by 8-SPT. There were no significant differences of collateral blood flow or risk area between the groups. We conclude that methotrexate and its derivative (MX-68) both limit infarct size via adenosine-dependent mechanisms.
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PMID:Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts. 1508 69

Increased transport of Na+ across an intact blood-brain barrier (BBB) participates in edema formation during the early hours of cerebral ischemia. In previous studies, the authors showed that the BBB Na-K-Cl cotransporter is stimulated by factors present during ischemia, suggesting that the cotransporter may contribute to the increased brain Na+ uptake in edema. The present study was conducted to determine (1) whether the Na-K-Cl cotransporter is located in the luminal membrane of the BBB, and (2) whether inhibition of the BBB cotransporter reduces brain edema formation. Perfusion-fixed rat brains were examined for cotransporter distribution by immunoelectron microscopy. Cerebral edema was evaluated in rats subjected to permanent middle cerebral artery occlusion (MCAO) by magnetic resonance diffusion-weighted imaging and calculation of apparent diffusion coefficients (ADC). The immunoelectron microscopy studies revealed a predominant (80%) luminal membrane distribution of the cotransporter. Magnetic resonance imaging studies showed ADC ratios (ipsilateral MCAO/contralateral control) ranging from 0.577 to 0.637 in cortex and striatum, indicating substantial edema formation. Intravenous bumetanide (7.6-30.4 mg/kg) given immediately before occlusion attenuated the decrease in ADC ratios for both cortex and striatum (by 40-67%), indicating reduced edema formation. Bumetanide also reduced infarct size, determined by TTC staining. These findings suggest that a luminal BBB Na-K-Cl cotransporter contributes to edema formation during cerebral ischemia.
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PMID:Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke. 1535 25

Triphenyltetrazolium chloride (TTC) and cresyl violet (CV) staining are routinely used methods to determine cerebral infarct volume and area. In this study, we compared these staining techniques using the mouse middle cerebral artery occlusion (MCAO) model of focal ischemia. Male C57BL6 mice were subjected to a 90 min transient MCAO and sacrificed at 24 h reperfusion. Sham operated mice served as controls. Two millimeters coronal brain slices were cut at +1.3, -0.7, -2.7 and -4.7 mm from bregma. The sections were stained with 2% TTC for 20 min and the caudal face of each slice was scanned with a flatbed scanner. The sections were kept in 4% paraformaldehyde solution for 4 weeks (the solution was changed every week). The slices were cryosectioned (40 microm thick), mounted on slides and stained with CV and scanned. The infarct volume and area were measured by the image-J program for both the staining techniques. There was no significant difference in either infarct area or volume between the TTC and CV stained sections (P > 0.05). TTC and CV staining showed a high degree of correlation in infarct area and volume indicating that both methods are suitable for producing accurate measurements of cerebral experimental infarcts.
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PMID:Infarct volume quantification in mouse focal cerebral ischemia: a comparison of triphenyltetrazolium chloride and cresyl violet staining techniques. 1548 33

Rodent models of stroke are often used to investigate the mechanisms that lead to ischemic neuronal damage. In this study, we used a model of cerebral hypoxia with ischemia to produce unilateral damage in C57Bl/6 mice. Lesion volume, ascertained by TTC staining, increased with longer durations of hypoxia. Additionally, cresyl violet, TUNEL, and FluoroJade staining showed a statistically significant increase in cellular damage in the ipsilateral cortex, CA1 pyramidal layer, and dentate gyrus of the hippocampus of ipsilateral hypoxic/ischemic tissue versus sham tissue. Astrocyte reactivity, determined by GFAP staining, was significantly higher in the ipsilateral H/I cortex and contralateral hippocampus compared to sham cortex and hippocampus, respectively. Increased microglia activation was evident in the H/I-treated cortex and hippocampus versus sham cortex and hippocampus, particularly within areas undergoing degeneration. To examine whether this model produces motor deficits, a battery of tests were administered before and after hypoxia. Following 45 min H/I, locomotor activity, rotarod performance and performance on an inverted wire hang test were all significantly decreased. These data indicate that the histological evidence of neuronal damage is consistent with functional deficits and suggest that this model may be useful for investigating strategies designed to protect neurons from hypoxia/ischemia-induced damage.
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PMID:Characterization of cellular and neurological damage following unilateral hypoxia/ischemia. 1554 86

The aim of the present study was to determine whether specific inhibition of mitochondrial permeability transition (MPT) by NIM811 at the time of reperfusion following acute myocardial infarction may protect the heart. MPT pore opening appears to be a pivotal event in cell death following acute myocardial infarction. Recently, MPT pore opening has been involved in ischemic preconditioning. In protocol 1, NZW rabbits underwent either no intervention (sham) or 10 min of ischemia followed by 5 min of reperfusion, preceded (preconditioned, PC) or not (control, C) by 5 min of ischemia and 5 min of reperfusion. Additional rabbits were treated by cyclosporin A (CsA) or its non-immunosuppressive and more specific derivative (NIM811) (10 mg kg(-1), IV bolus), either 10 min before ischemia or 1 min before reperfusion. Hearts were excised and mitochondria isolated for further assessment of Ca(2+)-induced MPT. In protocol 2, animals were randomly assigned into similar experimental groups and underwent 30 min of ischemia and 4 h of reperfusion. Infarct size was assessed by TTC staining, and apoptosis by TUNEL assay. The Ca2+ overload required to induce MPT pore opening was significantly higher in NIM811, CsA and PC groups than in controls. Both necrotic and apoptotic cardiomyocyte death were significantly reduced by NIM811, CsA and PC. In both protocols, administration of NIM811 at reperfusion provided full protection. These data indicate that specific inhibition of MPT pore opening at reperfusion following acute myocardial infarction provides a powerful antinecrotic and antiapoptotic protection.
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PMID:Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. 1569 43

The authors investigated the effects of phenylephrine-induced hypertension on the development of cerebral edema and neuronal dysfunction during focal cerebral ischemia. Mean arterial pressure was increased by 25-30 mm Hg immediately after middle cerebral artery occlusion (MCAO) in anesthetized rats. The increase was maintained for 3 h, at which time the brains were harvested and sectioned along coronal planes spanning the distribution of the MCA. The specific gravity (SG) was determined in specimens of cortex and subcortex. Brain sections adjacent to those used for SG measurement were incubated in 2,3,5-triphenyltetrazolium (TTC). There was edema formation in both groupsipsilateral to MCAO. However, in some regions, there was less edema accumulation in the induced hypertension group than in normotensive control animals. In adjacent regions, the area of reduced or absent TTC staining was also significantly less in the induced hypertension group. The data indicate that, in this model, induced hypertension established soon after the onset of ischemia can serve to reduce the area of histochemically detectable neuronal dysfunction, and that not only is edema formation not aggravated, but it is actually reduced.
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PMID:The influence of phenylephrine-induced hypertension during focal cerebral ischemia on the formation of brain edema. 1581 77

Combined functional, perfusion and diffusion magnetic resonance imaging (MRI) with a temporal resolution of 30 mins was performed on permanent and transient focal ischemic brain injury in rats during the acute phase. The apparent diffusion coefficient (ADC), baseline cerebral blood flow (CBF), and functional MRI (fMRI) blood-oxygen-level-dependent (BOLD), CBF, and CMRO(2) responses associated with CO(2) challenge and forepaw stimulation were measured. An automated cluster analysis of ADC and CBF data was used to track the spatial and temporal progression of different tissue types (e.g., normal, 'at risk,' and ischemic core) on a pixel-by-pixel basis. With permanent ischemia (n=11), forepaw stimulation fMRI response in the primary somatosensory cortices was lost, although vascular coupling (CO(2) response) was intact in some animals. Control experiments in which the right common carotid artery was ligated without causing a stroke (n=8) showed that the delayed transit time had negligible effect on the fMRI responses in the primary somatosensory cortices. With temporary (15-mins, n=8) ischemia, transient CBF and/or ADC declines were observed after reperfusion. However, no T(2) or TTC lesions were observed at 24 h except in two animals, which showed very small subcortical lesions. Vascular coupling and forepaw fMRI response also remained intact. Finally, comparison of the relative and absolute fMRI signal changes suggest caution when interpreting percent changes in disease states in which the baseline signals are physiologically altered; quantitative CBF fMRI are more appropriate measures. This approach provides valuable information regarding ischemic tissue viability, vascular coupling, and functional integrity associated with ischemic injury and could have potential clinical applications.
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PMID:Functional, perfusion and diffusion MRI of acute focal ischemic brain injury. 1585 31

High-resolution diffusion- (DWI) and perfusion-weighted (PWI) imaging may provide substantial benefits in accurate delineation of normal, ischemic, and at-risk tissue. We compared the capability of low (400 x 400 microm(2)) and high (200 x 200 microm(2)) spatial resolution imaging in characterizing the spatiotemporal evolution of the ischemic lesion in a permanent middle artery occlusion (MCAO) model in rats. Serial measurements of cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) were performed. Lesion volumes were calculated by using viability thresholds or by visual inspection, and correlated with infarct volume defined by TTC staining at 24 h after MCAO. At the very early phase of ischemia, high-resolution resulted in a significantly larger ADC-derived lesion volume and a smaller PWI/DWI mismatch. At 3 h after MCAO, ADC and CBF lesions showed similar robust correlations with TTC-defined infarct volumes for both groups using previously established thresholds. When lesions were determined visually, low-resolution resulted in a substantial overestimation of TTC-defined infarct volume and a lower inter-observer reliability (r = 0.75), whereas high-resolution produced an excellent correlation with TTC-defined infarct volume and inter-observer reliability (r = 0.96). In conclusion, high-resolution MRI resulted in substantial temporal averaging of the ischemic lesion during the early phase, but was clearly superior in visual determination of final infarct size. Low-resolution reasonably evaluated the temporal and spatial evolution of ischemia when thresholds were used.
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PMID:Perfusion and diffusion imaging in acute focal cerebral ischemia: temporal vs. spatial resolution. 1586 29

We here assessed the effects of 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, on infarct size in the rat heart subjected to ischemia/reperfusion. Rats were subjected to a 30-min coronary occlusion followed by a 24-h reperfusion. DY-9760e was intravenously infused for 20 min, starting at 20 min after coronary occlusion. Treatment with DY-9760e (10 mg/kg) significantly reduced the infarct size in the risk area assessed by Evans Blue/TTC (triphenyltetrazolium chloride) staining. DY-9760e treatment also ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion. DY-9760e significantly inhibited fodrin breakdown and caspase-3 activation. The inhibitory effect of DY-9760e on the fodrin breakdown was prominent in the rim rather than in the center of the risk area. DY-9760e also blocked protein tyrosine nitration associated with infarction. These results suggest that the cardioprotective effect of DY-9760e involved inhibition of calpain/caspase activation and protein tyrosine nitration.
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PMID:Cytoprotective effect of 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e) against ischemia/reperfusion-induced injury in rat heart involves inhibition of fodrin breakdown and protein tyrosine nitration. 1593 3


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