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

Loss of integrity of the blood-brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion-weighted imaging, T1-weighted (T1 W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B, n = 9), and 2 h 30 min (group C, n = 10). For 17 animals (four in group A, six in group B, and seven in group C), MnCl2 and dimeglumine gadoterate (Gd-DOTA) were injected at 13 min and 34 min after recanalization, respectively. The 10 remaining animals (control groups) underwent the same acquisition protocols, but no contrast agents were injected. Cell damage was determined 1 h after recanalization on haematoxylin and eosin-stained sections. Our results indicate that in the middle cerebral artery occlusion model in the rat, changes in BBB permeability assessed by contrast agent extravasation occur within the first hour of reperfusion, even after an occlusion period not exceeding 30 min. No differences between BBB permeability to Gd-DOTA and Mn2+ were detected in our experimental conditions. The reduction in apparent diffusion coefficient during occlusion appears to be a good predictor of BBB modifications after reperfusion in this model.
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PMID:Blood-brain barrier permeability to manganese and to Gd-DOTA in a rat model of transient cerebral ischaemia. 1794 22

This paper discusses the suitability of manganese for its function in catalysing the formation of molecular oxygen from water. Manganese is an abundant element. In terms of its inherent properties, Mn has a particularly rich redox chemistry compared with other d-block elements, with several oxidizing states accessible. The most stable-state Mn2+ behaves like a Group 2 element--it is mobile, weakly complexing, easily taken up by cells and redox-inactive in simple aqueous media. Only in the presence of suitable ligands does Mn2+ become oxidized, so it provides an uncomplicated building unit for the oxygen-evolving centre (OEC). The intermediate oxidation states Mn(III) and Mn(IV) are strongly complexed by O2(-) and form robust mixed-valence poly-oxo clusters in which the Mn(IV)/Mn(III) ratio can be elevated, one electron at a time, accumulating oxidizing potential and capacity. The OEC is a Mn4CaOx cluster that undergoes sequential oxidations by P680+ at potentials above 1V, ultimately to a super-oxidized level that includes one Mn(V) or a Mn(IV)-oxyl radical. The latter is powerfully oxidizing and provides the crucial 'power stroke' necessary to generate an O-O bond. This leaves a centre still rich in Mn(IV), ensuring a rapid follow-through to O2.
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PMID:Why did Nature choose manganese to make oxygen? 1797 29

Restoration of function after stroke may be associated with structural remodeling of neuronal connections outside the infarcted area. However, the spatiotemporal profile of poststroke alterations in neuroanatomical connectivity in relation to functional recovery is still largely unknown. We performed in vivo magnetic resonance imaging (MRI)-based neuronal tract tracing with manganese in combination with immunohistochemical detection of the neuronal tracer wheat-germ agglutinin horseradish peroxidase (WGA-HRP), to assess changes in intra- and interhemispheric sensorimotor network connections from 2 to 10 weeks after unilateral stroke in rats. In addition, functional recovery was measured by repetitive behavioral testing. Four days after tracer injection in perilesional sensorimotor cortex, manganese enhancement and WGA-HRP staining were decreased in subcortical areas of the ipsilateral sensorimotor network at 2 weeks after stroke, which was restored at later time points. At 4 to 10 weeks after stroke, we detected significantly increased manganese enhancement in the contralateral hemisphere. Behaviorally, sensorimotor functions were initially disturbed but subsequently recovered and plateaued 17 days after stroke. This study shows that manganese-enhanced MRI can provide unique in vivo information on the spatiotemporal pattern of neuroanatomical plasticity after stroke. Our data suggest that the plateau stage of functional recovery is associated with restoration of ipsilateral sensorimotor pathways and enhanced interhemispheric connectivity.
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PMID:Manganese-enhanced MRI of brain plasticity in relation to functional recovery after experimental stroke. 1798 47

Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries (MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Plasma levels of interleukin (IL)-6 and IL-1beta were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion (O(2)(.)) production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, O2. production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase (SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/reperfusion. However, N(omega)-nitro-l-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/reperfusion. Excessive production of O2. in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.
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PMID:Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion. 1825 83

Manganese-enhanced MRI (MEMRI) has been described as a powerful tool to depict the architecture of neuronal circuits. The aim of the present study was to optimize the experimental conditions of MEMRI that permits the study of insult-induced alterations of the somatosensory pathway in a longitudinal way, and to provide functional information on rat corticothalamic connectivity or disturbances thereof. A guidance screw was implanted in the skull of the rats, over the forelimb representation area of the primary somatosensory cortex (S1fl), allowing repetitive injections at the same stereotactic coordinates. MnCl2 (200 nL, 0.3 M) was injected 1.5 mm below the dura using a calibrated microcapillary. Animals received MnCl2 injections 3 times at 15 day intervals. Spatiotemporal patterns showed a significant hyperintensity on T1-weighted images induced by manganese transport in structures related to the somatosensory pathway, i.e. globus pallidus, caudate putamen, thalamus and substantia nigra. 7 days after MnCl2 injection hyperintensity was only evident at some points surrounding the injection site. Complete loss of manganese-induced contrast was achieved after 15 days after injection. Functional MRI (fMRI) experiments were performed under the same conditions, 24 h after MnCl2 injection. Activation of S1fl was observed showing that fMRI and MEMRI studies are compatible and can be performed in parallel in the same animals. The present study shows, for the first time, a robust and reproducible technique to perform longitudinal MEMRI (L-MEMRI) experiments and to study the time course of alterations of the corticothalamic connections following stroke in the rat.
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PMID:Reproducible imaging of rat corticothalamic pathway by longitudinal manganese-enhanced MRI (L-MEMRI). 1844 33

Spontaneous restoration of function after stroke is associated with remodelling of functional neuronal networks in and around the ischemic lesion. However, the spatiotemporal profile of structural alterations in (peri)lesional tissue in relation to post-stroke recovery of neuronal function remains largely to be elucidated. We performed neurological testing in combination with in vivo serial T(2)-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to assess functional recovery in relation to longitudinal changes in tissue integrity from 3 h up to 9 weeks after experimental unilateral stroke in rats (n=7). Subsequently, to evaluate perilesional neuronal connectivity, we conducted manganese-enhanced MRI after MnCl(2) injection in cortical tissue at the boundary of the lesion at 10 weeks post-stroke (n=5). All animals showed significant improvement of neurological function over time. Normalization of tissue T(2) and fractional diffusion anisotropy (FA) after significant subacute change was observed in cortical and subcortical lesion borderzones between 3 and 9 weeks post-stroke. Progressive FA increase above baseline levels was detected in perilesional white matter areas (n=4). In these animals particularly, significant manganese enhancement appeared within the neuronal network around the chronic lesion, including areas that were part of the lesion at day 3 post-stroke. This longitudinal multi-parametric MRI study suggests that resolution of early ischemic damage and reorganization of white matter in perilesional tissue is chronically accompanied by preservation or restoration of neuronal connectivity, which may significantly contribute to post-stroke functional recovery.
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PMID:Longitudinal in vivo MRI of alterations in perilesional tissue after transient ischemic stroke in rats. 1850 49

Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) signaling after stroke may reduce brain injury, but this effect will depend on the levels of receptor and cofactors. Here, we showed that the direct effect of PPARgamma signaling to protect neurons from ischemic injury requires a novel cofactor LMO4, because this effect was lost in LMO4-null cortical neurons. PPARgamma agonist also failed to reduce cerebral infarction after transient focal ischemia in CaMKIIalphaCre/LMO4loxP mice with LMO4 ablated in neurons of the forebrain. Expressing LMO4 in LMO4-null cortical neurons rescued the PPARgamma-protective effect. PPARgamma signaling activates the promoter of the antioxidant gene SOD2 and this process requires LMO4. Addition of a superoxide dismutase mimetic MnTBAP [manganese(III)tetrakis(4-benzoic acid)porphyrin] bypassed the deficiency in PPARgamma signaling and was able to directly rescue LMO4-null cortical neurons from ischemic injury. Like LMO4, PPARgamma and PGC1alpha (PPARgamma coactivator 1alpha) levels in neurons are elevated by hypoxic stress, and absence of LMO4 impairs their upregulation. Coimmunoprecipitation and mammalian two-hybrid assays revealed that LMO4 interacts in a ligand-dependent manner with PPARgamma. LMO4 augments PPARgamma-dependent gene activation, in part, by promoting RXRalpha (retinoid X receptor-alpha) binding to PPARgamma and by increasing PPARgamma binding to its target DNA sequence. Together, our results identify LMO4 as an essential hypoxia-inducible cofactor required for PPARgamma signaling in neurons. Thus, upregulation of LMO4 expression after stroke is likely to be an important determinant of neuron survival.
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PMID:Rescue of neurons from ischemic injury by peroxisome proliferator-activated receptor-gamma requires a novel essential cofactor LMO4. 1902 36

In this work, we report novel fibrin targeted "soft-type" manganese-based contrast agents for MRI with the potential to noninvasively image intravascular thrombus which could warrant aggressive medical intervention to preclude subsequent myocardial infarction or stroke.
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PMID:Sensitive and efficient detection of thrombus with fibrin-specific manganese nanocolloids. 1958 24

Reactive astrogliosis occurs after diverse central nervous system (CNS) insults. While astrogliosis provides protection against inflammation, it is also obstructive in the progress of neuranagenesis after CNS insults. Thus, a method that enables in vivo visualization and tissue characterization for gliosis would be invaluable for studies of CNS insults and corresponding treatments. Manganese has proven to be a useful MRI contrast agent that enters cells via Ca(2+) channels and has been applied to manganese-enhanced MRI (MEMRI) for neuronal functional mapping. This study investigated whether MEMRI can detect astrogliosis after focal ischemia in vivo. Rats were divided into groups according to the number of days after either transient middle cerebral artery occlusion or a sham. Ring- or crescent-shaped enhancement of MEMRI corresponded to the GFAP-positive astroglia observed in the peripheral region of the ischemic core 11 days after middle cerebral artery occlusion. This indicates that MEMRI enhancement predominantly reflects reactive astrogliosis after stroke.
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PMID:In vivo visualization of reactive gliosis using manganese-enhanced magnetic resonance imaging. 1990 19

Effective stroke therapies require recanalization of occluded cerebral blood vessels. However, reperfusion can cause neurovascular injury, leading to cerebral edema, brain hemorrhage, and neuronal death by apoptosis/necrosis. These complications, which result from excess production of reactive oxygen species in mitochondria, significantly limit the benefits of stroke therapies. We have developed a focal stroke model using mice deficient in mitochondrial manganese-superoxide dismutase (SOD2-/+) to investigate neurovascular endothelial damage that occurs during reperfusion. Following focal stroke and reperfusion, SOD2-/+ mice had delayed blood-brain barrier breakdown, associated with activation of matrix metalloproteinase and high brain hemorrhage rates, whereas a decrease in apoptosis and hemorrhage was observed in SOD2 overexpressors. Thus, induction and activation of SOD2 is a novel strategy for neurovascular protection after ischemia/reperfusion. Our recent study identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse SOD2 gene. During reperfusion, activation of STAT3 and its recruitment into the SOD2 gene were blocked, resulting in increased oxidative stress and neuronal apoptosis. In contrast, pharmacological activation of STAT3 induced SOD2 expression, which limits ischemic neuronal death. Our studies point to antioxidant-based neurovascular protective strategies as potential treatments to expand the therapeutic window of currently approved therapies.
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PMID:Reperfusion and neurovascular dysfunction in stroke: from basic mechanisms to potential strategies for neuroprotection. 2015 89


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