In situ immunoradiographic method for quantification of specific proteins in normal and ischemic brain regions

Rebel, Annette; Koehler, Raymond C.; Martin, Lee J.

doi:10.1016/j.jneumeth.2004.11.003

Cited by 10 publications

(8 citation statements)

References 31 publications

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“…quences of ischemia, 14 although stress proteins such as heat shock protein 70 are upregulated. 13 Correlations have been found between regions of expression of heat shock proteins and the penumbra, defined as the region of suppressed synthesis of proteins with preservation of adenosine 5Ј-triphosphate levels.…”

Section: The Ischemic Penumbra As a Biochemical Targetmentioning

confidence: 99%

Targeting the Ischemic Penumbra

Ramos‐Cabrer

Campos²,

Sobrino³

et al. 2011

Stroke

155

115

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Background— In the last 3 decades, and from a therapeutic point of view, the classical concept of ischemic penumbra based on hemodynamic and electrophysiological parameters has loosened up the rigidity of therapeutic windows in acute stroke management. Thirty years later, the ischemic penumbra is an evolved concept that presents more applications. Thus, the ischemic penumbra is a diagnostic target, allowing the extension of therapeutic windows; it is also a biochemical target, in which an intermittent bioenergetic compromise takes place, and it is a target for brain plasticity, neuroprotection, and neurorepair. Summary of Review— In this work, we review how the concept of ischemic penumbra has been evolving from its purely electrophysiological/ hemodynamic based definition to the wider metabolic–cellular–therapeutic concept that is managed today by neuroscientists.

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Section: The Ischemic Penumbra As a Biochemical Targetmentioning

confidence: 99%

Targeting the Ischemic Penumbra

Ramos‐Cabrer

Campos²,

Sobrino³

et al. 2011

Stroke

155

115

View full text Add to dashboard Cite

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“…This hypoxic redistribution was prevented when cells were cultured under hypoxic conditions but in the additional presence of 5 M SN50 (Fig. 7B, meostasis by astrocytes is key to normal synaptic neurotransmission and indeed to coordination of neural networks (Fellin et al, 2006), several studies have examined how such uptake is modulated by hypoxia/ischemia (Torp et al, 1995;Martin et al, 1997;Rao et al, 1998;Fujita et al, 1999;Gottlieb et al, 2000;Raghavendra et al, 2000;Tao et al, 2001;Rebel et al, 2005). However, although some of these studies have identified alterations in EAAT protein and mRNA levels, results are variable and no mechanism or functional consequences have been provided.…”

Section: Nf-b But Not Hypoxia-inducible Factor Mediates Hypoxic Supprmentioning

confidence: 99%

“…For example, amyotrophic lateral sclerosis has been linked to reduced levels of the GLT protein (Milton et al, 1997;Maragakis and Rothstein, 2004), although this is not uncontested (Fray et al, 1998). EAAT2 protein levels are reduced in the brain in various models of central ischemia and/or trauma (Torp et al, 1995;Martin et al, 1997;Rao et al, 1998;Raghavendra et al, 2000;Rebel et al, 2005). In contrast, the expression of EAAT1 and EAAT3 has been reported as either decreased (Martin et al, 1997;Fujita et al, 1999) or increased (Yan et al, 1998;Gottlieb et al, 2000;Tao et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Suppresses Glutamate Transport in Astrocytes

Dallas

Boycott²,

Atkinson³

et al. 2007

J. Neurosci.

103

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Glutamate uptake by astrocytes is fundamentally important in the regulation of CNS function. Disruption of uptake can lead to excitotoxicity and is implicated in various neurodegenerative processes as well as a consequence of hypoxic/ischemic events. Here, we investigate the effect of hypoxia on activity and expression of the key glutamate transporters excitatory amino acid transporter 1 (EAAT1) [GLAST (glutamate-aspartate transporter)] and EAAT2 [GLT-1 (glutamate transporter 1)]. Electrogenic, Na ϩ -dependent glutamate uptake was monitored via whole-cell patch-clamp recordings from cortical astrocytes. Under hypoxic conditions (2.5 and 1% O 2 exposure for 24 h), glutamate uptake was significantly reduced, and pharmacological separation of uptake transporter subtypes suggested that the EAAT2 subtype was preferentially reduced relative to the EAAT1. This suppression was confirmed at the level of EAAT protein expression (via Western blots) and mRNA levels (via real-time PCR). These effects of hypoxia to inhibit glutamate uptake current and EAAT protein levels were not replicated by desferrioxamine, cobalt, FG0041, or FG4496, agents known to mimic effects of hypoxia mediated via the transcriptional regulator, hypoxia-inducible factor (HIF). Furthermore, the effects of hypoxia were not prevented by topotecan, which prevents HIF accumulation. In stark contrast, inhibition of nuclear factor-B (NF-B) with SN50 fully prevented the effects of hypoxia on glutamate uptake and EAAT expression. Our results indicate that prolonged hypoxia can suppress glutamate uptake in astrocytes and that this effect requires activation of NF-B but not of HIF. Suppression of glutamate uptake via this mechanism may be an important contributory factor in hypoxic/ischemic triggered glutamate excitotoxicity.

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“…All the changes reviewed above also apply to a variable extent to these two zones, but with some unique events in the penumbra such as reduction in protein synthesis (Castellanos et al, 2006;Rebel et al, 2005). A complex interplay of these factors with reperfusion determines the ultimate outcome of the parenchyma in the penumbra zone (Hossmann, 2006).…”

Section: Changes In the Cerebral Vascular Response And Microcircumentioning

confidence: 99%

Regulation of cerebral vasculature in normal and ischemic brain

et al. 2008

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In the present review, we focus on the regulation of cerebral blood flow (CBF) and cerebral vasculature in the normal and ischemic brain, with a special emphasis on the arterial microcirculation of the brain: the pial and penetrating vessels. I. BackgroundThe cerebral circulation can be divided into categories based on a number of criteria. For example, vessel size can be utilized to divide the brain circulation into the macro-circulation and the microcirculation. On the arterial side, the former begins in the neck and extends to pial arteries. The microcirculation consists of the pial and penetrating arterioles, the capillaries and the venules. Within the arterial circulation, the major function of the macro-circulation is conductance of blood whereas the principal activity of the arterial component of the microcirculation is regulation of flow. Although the capillaries and venules are a significant contributor to cerebrovascular resistance, their role in regulation of flow is minimal under physiologic conditions. In addition to size, vessel location can be used to characterize the brain circulation. Thus, the brain vasculature can be divided in relation to the parenchyma into an extrinsic and an intrinsic component. The former encompasses the large conductance vessels (i.e., the macrocirculation) plus the pial circulation, whereas the latter consists of the intracerebral circulation composed of small arterioles, capillaries and venules. Penetrating arterioles represent the transition from the extrinsic to the intrinsic system. Clearly these two systems differ in regard to a number of features, such as proximity to the parenchyma, influence of neuronal and astrocytic activity, and presence and origin of innervation. However, despite these differences, both the extrinsic and intrinsic components of the cerebral circulation have an integrated response to cerebral challenges: co-dependency is the norm under physiologic and most pathologic conditions.

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In situ immunoradiographic method for quantification of specific proteins in normal and ischemic brain regions

Cited by 10 publications

References 31 publications

Targeting the Ischemic Penumbra

Targeting the Ischemic Penumbra

Hypoxia Suppresses Glutamate Transport in Astrocytes

Regulation of cerebral vasculature in normal and ischemic brain

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