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A novel, clinically relevant use of a piglet model to study the effects of anesthetics on the developing brain

Overview of attention for article published in Clinical and Translational Medicine, January 2016
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  • Above-average Attention Score compared to outputs of the same age (61st percentile)

Mentioned by

3 tweeters


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29 Mendeley
A novel, clinically relevant use of a piglet model to study the effects of anesthetics on the developing brain
Published in
Clinical and Translational Medicine, January 2016
DOI 10.1186/s40169-015-0079-9
Pubmed ID

Emmett E. Whitaker, Bruno Bissonnette, Andrew D. Miller, Tanner L. Koppert, Joseph D. Tobias, Christopher R. Pierson, Fievos L. Christofi


Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms of action may be undertaken. The goal of this study was to develop a novel, clinically relevant, translational way to use a piglet model to investigate anesthesia effects on the developing brain. 29 newborn piglets were assigned to either: (1) control (no intervention, n = 10); (2) lipopolysaccharide (LPS; positive inflammatory control, n = 9); or (3) isoflurane anesthesia (n = 10). Positive inflammatory control animals were given 100 mcg/kg LPS from Escherichia coli intraperitoneally (IP) on the same day as those receiving isoflurane. Isoflurane was administered for 3 h while care was taken to ensure human perioperative conditions. To establish a clinical scenario, each animal was intubated and monitored with pulse oximetry, invasive and non-invasive blood pressure, electrocardiogram, temperature, end-tidal CO2, anesthetic concentration, and iSTAT blood analysis. All animals were sacrificed after 48 h using transcardiac perfusion of ice-cold, heparinized phosphate buffered saline (PBS) followed by 4 % paraformaldehyde (PFA). Brains were collected and histopathological analysis focused on the entorhinal cortex looking for degenerative changes due to its critical role in learning and memory. Reliable identification of entorhinal cortex was achieved by using colored ink on the surface of the brains, which was then cross-referenced with microscopic anatomy. Hematoxylin & eosin-stained high-power fields was used to quantify cells. ImageJ™ (National Institutes of Health, Bethesda, MD, USA) was used to count absolute number of progenitor glial cells (PGC) and number of PGCs per cluster. Immunohistochemistry was also utilized to ensure positive identification of cellular structures. Histopathological sections of 28 brains were analyzed. One animal in the LPS group died shortly after administration, presumably from inadvertent intravascular injection. There was an acute basal ganglia ischemic infarct in one isoflurane-treated animal. A large number of small, round nucleated cells were seen throughout layer II of the entorhinal cortex in all animals. These cells were identified as PGCs using immunohistochemistry and light microscopy. Although there was no difference in the absolute number of PGCs between the groups, animals given isoflurane or LPS demonstrated a significant increase in cells forming 'clusters' in the entorhinal cortex. An apparent change in the pattern of doublecortin labeling also suggests changes in neuronal precursors and undifferentiated neurons. This study represents the first novel use of a clinically relevant neonatal piglet model to study anesthesia effects on the developing brain. LPS induces neuroinflammation, and this is a potential mechanism for LPS and perhaps isoflurane in causing a change in progenitor cell distribution. We postulate that the isoflurane-induced change in glial progenitor cell distribution could have important implications for cell differentiation, maturation and neural circuit behavior in the rapidly developing brain.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 17%
Researcher 4 14%
Other 3 10%
Student > Ph. D. Student 3 10%
Professor > Associate Professor 3 10%
Other 7 24%
Unknown 4 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 21%
Medicine and Dentistry 5 17%
Neuroscience 4 14%
Nursing and Health Professions 2 7%
Engineering 2 7%
Other 5 17%
Unknown 5 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 February 2016.
All research outputs
of 15,640,884 outputs
Outputs from Clinical and Translational Medicine
of 246 outputs
Outputs of similar age
of 342,692 outputs
Outputs of similar age from Clinical and Translational Medicine
of 1 outputs
Altmetric has tracked 15,640,884 research outputs across all sources so far. This one is in the 45th percentile – i.e., 45% of other outputs scored the same or lower than it.
So far Altmetric has tracked 246 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.9. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 342,692 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them