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Inhibition of astrocyte metabolism is not the primary mechanism for anaesthetic hypnosis.

Voss LJ, Harvey MG, Sleigh JW - Springerplus (2016)

Bottom Line: Subsequently, the effect of astrocyte metabolic inhibition was investigated in neocortical slices, and compared with that of the anaesthetic drugs.In vivo anaesthetic potency correlated strongly with the magnitude of reduction in SLE frequency in neocortical slices (R(2) 37.7 %, p = 0.002).The capacity of an anaesthetic agent to reduce SLE frequency in the neocortical slice is a good indicator of its in vivo hypnotic potency.

View Article: PubMed Central - PubMed

Affiliation: Anaesthesia Department, Waikato District Health Board, Pembroke St, Hamilton, 3240 New Zealand.

ABSTRACT
Astrocytes have been promoted as a possible mechanistic target for anaesthetic hypnosis. The aim of this study was to explore this using the neocortical brain slice preparation. The methods were in two parts. Firstly, multiple general anaesthetic compounds demonstrating varying in vivo hypnotic potency were analysed for their effect on "zero-magnesium" seizure-like event (SLE) activity in mouse neocortical slices. Subsequently, the effect of astrocyte metabolic inhibition was investigated in neocortical slices, and compared with that of the anaesthetic drugs. The rationale was that, if suppression of astrocytes was both necessary and sufficient to cause hypnosis in vivo, then inhibition of astrocytic metabolism in slices should mimic the anaesthetic effect. In vivo anaesthetic potency correlated strongly with the magnitude of reduction in SLE frequency in neocortical slices (R(2) 37.7 %, p = 0.002). Conversely, SLE frequency and length were significantly enhanced during exposure to both fluoroacetate (23 and 20 % increase, respectively, p < 0.01) and aminoadipate (12 and 38 % increase, respectively, p < 0.01 and p < 0.05). The capacity of an anaesthetic agent to reduce SLE frequency in the neocortical slice is a good indicator of its in vivo hypnotic potency. The results do not support the hypothesis that astrocytic metabolic inhibition is a mechanism of anaesthetic hypnosis.

No MeSH data available.


Related in: MedlinePlus

Effect of 0.5 (n = 17), 1.0 (n = 13) and 5.0 mM (n = 8) aminoadipic acid on seizure-like event a frequency, b length and c amplitude. The data are normalised to baseline values and are expressed as mean + SEM. *p < 0.05, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons. **p < 0.01, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons
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Fig4: Effect of 0.5 (n = 17), 1.0 (n = 13) and 5.0 mM (n = 8) aminoadipic acid on seizure-like event a frequency, b length and c amplitude. The data are normalised to baseline values and are expressed as mean + SEM. *p < 0.05, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons. **p < 0.01, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons

Mentions: The 0.5 mM dose of aminoadipic had an effect similar to that of fluoroacetate, with a significant, reversible increase in SLE frequency and length (see Figs. 4, 5). The 1.0 and 5.0 mM doses had biphasic effects, with an initial excitation (increase in SLE frequency), coupled with a reduction in event length and amplitude. SLE activity was reversibly silenced at 5.0 mM following a brief surge in event frequency. These effects are illustrated in Figs. 4 and 5.Fig. 4


Inhibition of astrocyte metabolism is not the primary mechanism for anaesthetic hypnosis.

Voss LJ, Harvey MG, Sleigh JW - Springerplus (2016)

Effect of 0.5 (n = 17), 1.0 (n = 13) and 5.0 mM (n = 8) aminoadipic acid on seizure-like event a frequency, b length and c amplitude. The data are normalised to baseline values and are expressed as mean + SEM. *p < 0.05, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons. **p < 0.01, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940352&req=5

Fig4: Effect of 0.5 (n = 17), 1.0 (n = 13) and 5.0 mM (n = 8) aminoadipic acid on seizure-like event a frequency, b length and c amplitude. The data are normalised to baseline values and are expressed as mean + SEM. *p < 0.05, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons. **p < 0.01, compared to baseline, Friedman Test with Dunn’s Multiple Comparisons
Mentions: The 0.5 mM dose of aminoadipic had an effect similar to that of fluoroacetate, with a significant, reversible increase in SLE frequency and length (see Figs. 4, 5). The 1.0 and 5.0 mM doses had biphasic effects, with an initial excitation (increase in SLE frequency), coupled with a reduction in event length and amplitude. SLE activity was reversibly silenced at 5.0 mM following a brief surge in event frequency. These effects are illustrated in Figs. 4 and 5.Fig. 4

Bottom Line: Subsequently, the effect of astrocyte metabolic inhibition was investigated in neocortical slices, and compared with that of the anaesthetic drugs.In vivo anaesthetic potency correlated strongly with the magnitude of reduction in SLE frequency in neocortical slices (R(2) 37.7 %, p = 0.002).The capacity of an anaesthetic agent to reduce SLE frequency in the neocortical slice is a good indicator of its in vivo hypnotic potency.

View Article: PubMed Central - PubMed

Affiliation: Anaesthesia Department, Waikato District Health Board, Pembroke St, Hamilton, 3240 New Zealand.

ABSTRACT
Astrocytes have been promoted as a possible mechanistic target for anaesthetic hypnosis. The aim of this study was to explore this using the neocortical brain slice preparation. The methods were in two parts. Firstly, multiple general anaesthetic compounds demonstrating varying in vivo hypnotic potency were analysed for their effect on "zero-magnesium" seizure-like event (SLE) activity in mouse neocortical slices. Subsequently, the effect of astrocyte metabolic inhibition was investigated in neocortical slices, and compared with that of the anaesthetic drugs. The rationale was that, if suppression of astrocytes was both necessary and sufficient to cause hypnosis in vivo, then inhibition of astrocytic metabolism in slices should mimic the anaesthetic effect. In vivo anaesthetic potency correlated strongly with the magnitude of reduction in SLE frequency in neocortical slices (R(2) 37.7 %, p = 0.002). Conversely, SLE frequency and length were significantly enhanced during exposure to both fluoroacetate (23 and 20 % increase, respectively, p < 0.01) and aminoadipate (12 and 38 % increase, respectively, p < 0.01 and p < 0.05). The capacity of an anaesthetic agent to reduce SLE frequency in the neocortical slice is a good indicator of its in vivo hypnotic potency. The results do not support the hypothesis that astrocytic metabolic inhibition is a mechanism of anaesthetic hypnosis.

No MeSH data available.


Related in: MedlinePlus