Physiological Evidence That Pyramidal Neurons Lack Functional Water Channels

Andrew, R. David; Labron, Mark W.; Boehnke, Susan E.; Carnduff, Lisa; Kirov, Sergei A.

doi:10.1093/cercor/bhk032

Cited by 157 publications

(272 citation statements)

References 64 publications

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“…Cell volume changes have also been reported in ischemia, stroke (Fig. 8), osmotic modulation, and spreading depression (37,42,44,57); in all of these instances, diffusionweighted MRI shows a positive response (40,41,61). Thus, cell swelling may contribute to the reduced water diffusivity observed here and in other pathological states mentioned above.…”

Section: Discussionsupporting

confidence: 78%

“…Although differences exist between this in vitro system and the in vivo case, similar findings in the stroke model as in vivo studies provide additional evidence that the organotypic culture system mimics well-known behaviors observed in mammalian brains in vivo. A phenomenon of cell swelling induced by intense neuronal depolarization has been reported in other imaging studies (37,44,(56)(57)(58)(59)(60). Cell volume changes have also been reported in ischemia, stroke (Fig.…”

Section: Discussionsupporting

confidence: 67%

“…Cell swelling has also been reported to occur during normal neuronal activity, but with a negligible amplitude that is much smaller than that caused by prolonged and strong depolarization (44,56,(65)(66)(67)(68). In general, the displacements of the cell surface are on the length scale of nanometers, with a maximum displacement of several tens of nanometers, under normal electrical stimulation (65)(66)(67)(68).…”

Section: Discussionmentioning

confidence: 99%

“…In general, the displacements of the cell surface are on the length scale of nanometers, with a maximum displacement of several tens of nanometers, under normal electrical stimulation (65)(66)(67)(68). However, the surface displacement changes in the neuronal soma induced by prolonged depolarization can be ≥∼1 μm (44,56,57). Therefore, it is unlikely that diffusion MRI is sensitive enough to measure the minor changes caused by normal neuronal activity, which are several orders of magnitude smaller than the changes observed in prolonged depolarization.…”

Section: Discussionmentioning

confidence: 99%

“…Another phenomenon associated with ischemia caused by acute stroke is depolarization of the cell membrane and calcium uptake by neurons (42,43). To assess the effects of these two phenomena, a stroke model using an oxygen/glucose deprivation (OGD) protocol was tested (37,41,44). In the OGD protocol, the glucose was deprived (NaCl was added to maintain constant osmotic pressure) and the ACSF was kept saturated with 95% N 2 + 5% O 2 .…”

Section: Diffusion Mr In a Pathological Stroke Model Via Oxygen/glucosementioning

confidence: 99%

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Assessing the sensitivity of diffusion MRI to detect neuronal activity directly

Bai

Stewart

Plenz

et al. 2016

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

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Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.D eveloping a direct MRI method to detect neuronal activity in vivo and noninvasively is a major focus in neuroscience. Progress in this area is required to improve our understanding of normal brain function, and in a clinical setting, to develop new tools for studying normal and abnormal development to diagnose diseases and disorders of the brain. Functional MRI (fMRI) has been widely used in the cognitive neurosciences since its invention in the 1990s (1-3). The most widely used fMRI method, blood-oxygenation-level-dependent (BOLD) MRI, detects hemodynamic changes in the brain, which only indirectly reflects neuronal activity. Moreover, its hemodynamic origin limits both its spatial and temporal resolution and its interpretation as a direct proxy for neuronal activity (4, 5).More recently, several MRI methods were proposed to provide more direct measures of neuronal excitation (6). In particular, diffusion MRI, a method to measure the apparent diffusivity of water within tissues (7-9), has been suggested as a direct functional imaging method to detect neuronal activity (10-13). Early in vivo experiments in both humans and animals reported small but significant increases in highly diffusion-weighted MRI signals, which were ascribed to changes directly induced by the underlying neuronal activity rather than indirect hemodynamic changes (10-13).In vitro experimen...

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Diffusion Mr In a Pathological Stroke Model Via Oxygen/glucosementioning

confidence: 99%

See 3 more Smart Citations

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly

Bai

Stewart

Plenz

et al. 2016

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

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Anion channels in astrocytes: Biophysics, pharmacology, and function

Kimelberg

MacVicar

Sontheimer

2006

Glia

112

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The chloride/anion channels that have been so far identified in cultured astrocytes and those that have been confirmed in situ by a combination of mRNA identification, immunocyto-chemistry, and biophysical studies are reviewed. It is emphasized that we are just beginning to describe such channels and analyze their functions in astrocytes. The best-studied anion channels studied so far are those known as volume-regulated anion channels (VRACs). These, as for most channels, have been mainly studied in cultured astrocytes, but some correlative studies have been done in situ, because these channels have been emphasized as release routes for transmitters; namely, excitatory amino acids and ATP. They are activated by cell shape changes and cell swelling, and the release of amino acids and ATP and chloride currents, measured by whole cell clamping, by these processes has been well described, as is also their activation by low concentrations of extracellular ATP. However, the identity of these channels in astrocytes, as in all other cells, remains elusive. The potential involvement of VRACs in pathological states such as stroke, metastasis, and spreading depression is also discussed.

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Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices

Reinehr

Görg

Becker

et al. 2007

Glia

186

142

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The role of NADPH oxidase (NOX) and the regulatory subunit p47(phox) for hypoosmotic ROS generation was studied in cultured rat astrocytes and brain slices of wilde type and p47(phox) knock-out mice. Cultured rat astrocytes express mRNAs encoding for the regulatory subunit p47(phox), NOX1, 2, and 4, and the dual oxidases (DUOX)1 and 2, but not NOX3. Hypoosmotic (205 mosmol/L) swelling of cultured astrocytes induced a rapid generation of ROS that was accompanied by serine phosphorylation of p47(phox) and prevented by the NADPH oxidase inhibitor apocynin. Apocynin also impaired the hypoosmotic tyrosine phosphorylation of Src. Both, hypoosmotic ROS generation and p47(phox) serine phosphorylation were sensitive to the acidic sphingomyelinase inhibitors AY9944 and desipramine, the protein kinase C (PKC)zeta-inhibitory pseudosubstrate peptide, the NMDA receptor antagonist MK-801 and the intracellular Ca(2+) chelator BAPTA-AM. Also hypoosmotic exposure of wilde type mouse cortical brain slices increased ROS generation, which was allocated in part to the astrocytes and which was absent in presence of apocynin and in cortical brain slices from p47(phox) knock-out mice. Also ammonia induced a rapid ROS production in cultured astrocytes and brain slices, which was sensitive to apocynin. The data suggest that astrocyte swelling triggers a p47(phox)-dependent NADPH oxidase-catalyzed ROS production. The findings further support a close interrelation between osmotic and oxidative stress in astrocytes, which may be relevant to different brain pathologies including hepatic encephalopathy.

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Physiological Evidence That Pyramidal Neurons Lack Functional Water Channels

Cited by 157 publications

References 64 publications

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly

Assessing the sensitivity of diffusion MRI to detect neuronal activity directly

Anion channels in astrocytes: Biophysics, pharmacology, and function

Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices

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