Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and α-chloralose anesthesia

Austin, V. C.; Blamire, Andrew M.; Allers, Kelly A.; Sharp, Trevor; Styles, Peter; Matthews, Paul M.; Sibson, Nicola R.

doi:10.1016/j.neuroimage.2004.08.011

Cited by 127 publications

(102 citation statements)

References 27 publications

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“…These human and animal studies suggest that the mismatch ratio and general glucose metabolism may depend on many criteria such as: age of the subject (Kalpouzos et al, 2009;Nelhig, 1997), brain regions, methodology, stimulus frequency (Vafaee and Gjedde, 2000;Vafaee et al, 1999) and duration (Herman et al, 2009;Mintun et al, 2002), basal metabolic status (Shen et al, 2008;Sicard and Duong, 2005) and the use of anesthesia (Austin et al, 2005;Dienel, 2012;Kim et al, 2010). Finally, (Dienel, 2012) reviewed that different stimulus paradigm increase CMR Glc with different rates.…”

Section: Discussionmentioning

confidence: 99%

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Xin²,

et al. 2014

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a b s t r a c t a r t i c l e i n f oRecent studies at high field (7 Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3 μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and good magnetic resonance spectroscopy (MRS) sensitivity using surface coil. The aim of this study was to extend functional MRS (fMRS) to investigate for the first time the metabolite changes during motor activation at 7 T. Small but sustained increases in lactate (0.17 μmol/g ± 0.05 μmol/g, p b 0.001) and glutamate (0.17 μmol/g ± 0.09 μmol/g, p b 0.005) were detected during motor activation followed by a return to the baseline after the end of activation. The present study demonstrates that increases in lactate and glutamate during motor stimulation are small, but similar to those observed during visual stimulation. From the observed glutamate and lactate increase, we inferred that these metabolite changes may be a general manifestation of the increased neuronal activity. In addition, we propose that the measured metabolite concentration increases imply an increase in ΔCMR O2 that is transiently below that of ΔCMR Glc during the first 1 to 2 min of the stimulation.© 2014 Elsevier Inc. All rights reserved. IntroductionFunctional MR spectroscopy (fMRS) provides direct insights into brain metabolism by investigating the metabolic response of the brain to a physiological stimulus. The high spectral resolution and signal-tonoise ratio (SNR) of fMRS at high field (N3 Tesla) improve the accuracy and precision of the quantification of many brain metabolites (Mekle et al., 2009;Tkac et al., 2001Tkac et al., , 2009. In addition to the increased chemical shift dispersion, a high time resolution is of advantage for the characterization of the small transient changes observed. Recent fMRS studies (Lin et al., 2012;Mangia et al., 2007b;Schaller et al., 2013) at high field (7 Tesla) reported small metabolite concentration changes during visual stimulation (around 0.2 μmol/g). In particular, a very small lactate concentration increase between 10 and 23% has been observed. Recently, functional diffusion-weighted MRS has been used to investigate metabolite ADC changes as a potential consequence of micro structural changes during activation (Branzoli et al., 2013).The lactate increase observed during visual stimulation has been suggested to explain the mismatch of cerebral metabolic rate of change for glucose (ΔCMR Glc ) (or cerebral blood flow, CBF) and cerebral metabolic rate of change for oxygen (ΔCMR O2 ) during brain activation. However, many studies have reported different results concerning the transient mismatch of ΔCMR Glc , CBF and ΔCMR O2 during functional activity (reviewed in Buxton (2010)). The characterization of these changes has been reported in positron emission tomography (PET) (Fox and

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Section: Discussionmentioning

confidence: 99%

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Xin²,

et al. 2014

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“…The user must be aware of the disadvantages when using anaesthetics; alpha chloralose decreases cerebral blood flow (Austin et al, 2005) and along with respiratory depression.…”

Section: Discussionmentioning

confidence: 99%

“…However it decreases cerebral blood flow (Austin et al, 2005), and due to its toxic nature it cannot be used for recovery experiments making it unsuitable for longitudinal studies (Silverman and Muir, 1993).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat

et al. 2010

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M., Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat, NeuroImage (2010), doi: 10.1016/j.neuroimage. 2010.03.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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“…The current delivered by each stimulator was measured before each the experiments to ensure identical stimulations of both paws. fMRI responses are highly sensitive to many factors, including blood pH, gas tensions, and the level of anesthesia (Austin et al, 2005;Franceschini et al, 2010). To ensure identical conditions when fMRI responses were triggered in hemispheres expressing TMPAP and EGFP, simultaneous bilateral forepaw stimulation was applied.…”

Section: Methodsmentioning

confidence: 99%

A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses

et al. 2015

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The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A 1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature.

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Confounding effects of anesthesia on functional activation in rodent brain: a study of halothane and α-chloralose anesthesia

Cited by 127 publications

References 27 publications

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Propofol allows precise quantitative arterial spin labelling functional magnetic resonance imaging in the rat

A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses

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