Intracerebral microdialysis of adenosine and adenosine monophosphate – a systematic review and meta‐regression analysis of baseline concentrations

Abstract

Microdialysis is a method to study the extracellular space in vivo, based on the principle of diffusion. It can be used to measure various small molecules including the neuroregulator adenosine. Baseline levels of the compounds measured with microdialysis vary over studies. We systematically reviewed the literature to investigate the full range of reported baseline concentrations of adenosine and adenosine monophosphate in microdialysates. We performed a meta‐regression analysis to study the influence of flow rate, probe membrane surface area, species, brain area and anaesthesia versus freely behaving, on the adenosine concentration. Baseline adenosine concentrations in microdialysates ranged from 0.8 to 2100 nM. There was limited evidence on baseline adenosine monophosphate concentrations in microdialysates. Across studies, we found effects of flow rate and anaesthesia versus freely behaving on dialysate adenosine concentrations (p ≤ 0.001), but not of probe membrane surface, species, or brain area (p ≥ 0.14). With increasing flow rate, adenosine concentrations decreased. With anaesthesia, adenosine concentrations increased. The effect of other predictor variables on baseline adenosine concentrations, for example, post‐surgical recovery time, could not be analysed because of a lack of reported data. This study shows that meta‐regression can be used as an alternative to new animal experiments to answer research questions in the field of neurochemistry. However, current levels of reporting of primary studies are insufficient to reach the full potential of this approach; 63 out of 133 studies could not be included in the analysis because of insufficient reporting, and several potentially relevant factors had to be excluded from the analyses. The level of reporting of experimental detail needs to improve.

Intracerebral Adenosine During Sleep Deprivation: A Meta-Analysis and New Experimental Data

“…The median adenosine concentration over the remaining 601 samples was 0.36 nM and the values found ranged from a minimum of 0.004 nM to a maximum of 27 nM. This is within the range of reported concentrations in our preceding systematic review [28]. Preliminary analyses of time curves, depicted in Figure 1, indicated high variability in some rats.…”

“…Within our previously described sample of 132 adenosine microdialysis studies [28], we identified nine papers measuring microdialysate adenosine levels during sleep deprivation. Eight of these papers (described in Table 1) reported dialysate adenosine concentrations during sleep deprivation and prior baseline, one [36] directly compared concentrations between groups only and could not be included in the meta-analyses.…”

“…We previously performed an SR on adenosine concentrations in microdialysates analysing the effects of variations in the experimental design on baseline concentrations [28]. The search and inclusion criteria for the preceding review were designed to capture all studies measuring intracerebral adenosine by microdialysis in animals.…”

“…In this paper we describe an experiment determining the effect of 12 h of sleep deprivation on mPFC adenosine concentrations. Besides, we performed a meta-analysis of sleep deprivation studies [28]. …”

“…A meta-analysis performed in combination with a full systematic review (SR) is considered to provide the highest possible level of evidence to answer a research question. We recently completed an SR analysing adenosine and AMP baseline concentrations in microdialysates in relation to the experimental design [28]. In that review, we included several studies on the effect of sleep deprivation on adenosine, which are analysed in this paper.…”