High-Resolution<i>In Vivo</i>Imaging of the Neurovascular Unit during Spreading Depression

Chuquet, Julien; Hollender, Liad; Nimchinsky, Esther A.

doi:10.1523/jneurosci.0721-07.2007

Cited by 192 publications

(208 citation statements)

References 57 publications

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“…In comparison, in our model, depolarizations initiated within the core had to spread through otherwise healthy surrounding tissue which may account for their slower rate. On the other hand, in vivo, AD propagation has also been shown to be around 1-2 mm/min (Somjen, 2001;Chuquet et al, 2007), which is much quicker than with our in vitro model. In vivo the region surrounding the core of a stroke continues to be perfused with blood; however, this perfusion is limited, thus stressing the tissue.…”

Section: Discussioncontrasting

confidence: 55%

A novel method for inducing focal ischemia in vitro

Richard

Saleh

Bahh³

et al. 2010

Journal of Neuroscience Methods

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Current in vitro models of stroke involve applying oxygen-glucose deprived (OGD) media over an entire brain slice or plate of cultured neurons. Thus, these models fail to mimic the focal nature of stroke as observed clinically and with in vivo rodent models of stroke. Our aim was to develop a novel in vitro brain slice model of stroke that would mimic focal ischemia and thus allow for the investigation of events occurring in the penumbra. This was accomplished by focally applying OGD medium to a small portion of a brain slice while bathing the remainder of the slice with normal oxygenated media. This technique produced a focal infarct on the brain slice that increased as a function of time. Electrophysiological recordings made within the flow of the OGD solution ("core") revealed that neurons rapidly depolarized (anoxic depolarization; AD) in a manner similar to that observed in other stroke models. Edaravone, a known neuroprotectant, significantly delayed this onset of AD. Electrophysiological recordings made outside the flow of the OGD solution ("penumbra") revealed that neurons within this region progressively depolarized throughout the 75 min of OGD application. Edaravone attenuated this depolarization and doubled neuronal survival. Finally, synaptic transmission in the penumbra was abolished within 50 min of focal OGD application. These results suggest that this in vitro model mimics events that occur during focal ischemia in vivo and can be used to determine the efficacy of therapeutics that target neuronal survival in the core and/or penumbra.

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Section: Discussioncontrasting

confidence: 55%

A novel method for inducing focal ischemia in vitro

Richard

Saleh

Bahh³

et al. 2010

Journal of Neuroscience Methods

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“…G-CaMP2 also provided a means of obtaining measurements without acute introduction of a dye-containing electrode, which could damage tissue. The fact that a less invasive approach yielded repeated ellipsoidal waves indicates that they are not pathological, unlike spreading depression, another wave-like phenomenon seen in neocortical (14,15) and cerebellar (13) astrocytes that differs by being independent of purinergic receptor activation (13), having higher speeds (Ͼ15 m/s), and a spatial range of millimeters. Waves recurred in the same location, but were not restricted to functional domains, because waves with spatially segregated initiation centers could overlap.…”

Section: Discussionmentioning

confidence: 99%

“…Spreading astrocytic waves can be triggered by focal electrical stimulation in brain slices (10) and by ATP release in culture (3,11). Glial waves have been observed in radial glia in the developing neocortex (12) and in models of spreading depression (13)(14)(15).…”

mentioning

confidence: 99%

Radially expanding transglial calcium waves in the intact cerebellum

Hoogland

Kühn

Göbel

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

148

133

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Multicellular glial calcium waves may locally regulate neural activity or brain energetics. Here, we report a diffusion-driven astrocytic signal in the normal, intact brain that spans many astrocytic processes in a confined volume without fully encompassing any one cell. By using 2-photon microscopy in rodent cerebellar cortex labeled with fluorescent indicator dyes or the calcium-sensor protein G-CaMP2, we discovered spontaneous calcium waves that filled approximately ellipsoidal domains of Bergmann glia processes. Waves spread in 3 dimensions at a speed of 4 -11 m/s to a diameter of Ϸ50 m, slowed during expansion, and were reversibly blocked by P2 receptor antagonists. Consistent with the hypothesis that ATP acts as a diffusible trigger of calcium release waves, local ejection of ATP triggered P2 receptor-mediated waves that were refractory to repeated activation. Transglial waves represent a means for purinergic signals to act with local specificity to modulate activity or energetics in local neural circuits.astrocytes ͉ Bergmann glia ͉ in vivo ͉ 2-photon microscopy ͉ G-CaMP2

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“…Another important question concerns the way in which those changes are communicated to the local microvasculature; experimental data suggest that astrocytes are likely to play a key role in this connection (Zonta et al, 2003;Jakovcevic and Harder 2007). Supporting results were recently obtained by two-photon microscopy, a particularly valuable technique in this context owing to its high spatial resolution (Mulligan and MacVicar, 2004;Takano et al, 2006;Chuquet et al, 2007). Other glial cells (in isolated retina: Metea and Newman, 2006) and interneurons (in cortical slices: Cauli B et al, 2004) evidently also play an important role in neurovascular coupling.…”

Section: Implications For Modeling Cerebral Haemodynamics and Oxygenmentioning

confidence: 91%

Coupling between neuronal activity and microcirculation: Implications for functional brain imaging

Vanzetta

Grinvald

2008

HFSP Journal

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In the neocortex, neurons with similar response properties are often clustered together in column-like structures, giving rise to what has become known as functional architecture-the mapping of various stimulus feature dimensions onto the cortical sheet. At least partially, we owe this finding to the availability of several functional brain imaging techniques, both post-mortem and in-vivo, which have become available over the last two generations, revolutionizing neuroscience by yielding information about the spatial organization of active neurons in the brain. Here, we focus on how our understanding of such functional architecture is linked to the development of those functional imaging methodologies, especially to those that image neuronal activity indirectly, through metabolic or haemodynamic signals, rather than directly through measurement of electrical activity. Some of those approaches allow exploring functional architecture at higher spatial resolution than others. In particular, optical imaging of intrinsic signals reaches the striking detail of È50 m, and, together with other methodologies, it has allowed characterizing the metabolic and haemodynamic responses induced by sensory-evoked neuronal activity. Here, we review those findings about the spatio-temporal characteristics of neurovascular coupling and discuss their implications for functional brain imaging, including position emission tomography, and non-invasive neuroimaging techniques, such as funtional magnetic resonance imaging, applicable also to the human brain.

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High-ResolutionIn VivoImaging of the Neurovascular Unit during Spreading Depression

Cited by 192 publications

References 57 publications

A novel method for inducing focal ischemia in vitro

A novel method for inducing focal ischemia in vitro

Radially expanding transglial calcium waves in the intact cerebellum

Coupling between neuronal activity and microcirculation: Implications for functional brain imaging

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