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HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy

Overview of attention for article published in Journal of Neuroinflammation, March 2023
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Title
HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy
Published in
Journal of Neuroinflammation, March 2023
DOI 10.1186/s12974-023-02756-3
Pubmed ID
Authors

Xiao-Yu Yin, Xiao-Hui Tang, Shi-Xu Wang, Yong-Chang Zhao, Min Jia, Jian-Jun Yang, Mu-Huo Ji, Jin-Chun Shen

Abstract

Microglial activation-mediated neuroinflammation is one of the essential pathogenic mechanisms of sepsis-associated encephalopathy (SAE). Mounting evidence suggests that high mobility group box-1 protein (HMGB1) plays a pivotal role in neuroinflammation and SAE, yet the mechanism by which HMGB1 induces cognitive impairment in SAE remains unclear. Therefore, this study aimed to investigate the mechanism of HMGB1 underlying cognitive impairment in SAE. An SAE model was established by cecal ligation and puncture (CLP); animals in the sham group underwent cecum exposure alone without ligation and perforation. Mice in the inflachromene (ICM) group were continuously injected with ICM intraperitoneally at a daily dose of 10 mg/kg for 9 days starting 1 h before the CLP operation. The open field, novel object recognition, and Y maze tests were performed on days 14-18 after surgery to assess locomotor activity and cognitive function. HMGB1 secretion, the state of microglia, and neuronal activity were measured by immunofluorescence. Golgi staining was performed to detect changes in neuronal morphology and dendritic spine density. In vitro electrophysiology was performed to detect changes in long-term potentiation (LTP) in the CA1 of the hippocampus. In vivo electrophysiology was performed to detect the changes in neural oscillation of the hippocampus. CLP-induced cognitive impairment was accompanied by increased HMGB1 secretion and microglial activation. The phagocytic capacity of microglia was enhanced, resulting in aberrant pruning of excitatory synapses in the hippocampus. The loss of excitatory synapses reduced neuronal activity, impaired LTP, and decreased theta oscillation in the hippocampus. Inhibiting HMGB1 secretion by ICM treatment reversed these changes. HMGB1 induces microglial activation, aberrant synaptic pruning, and neuron dysfunction in an animal model of SAE, leading to cognitive impairment. These results suggest that HMGB1 might be a target for SAE treatment.

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

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Postgraduate 2 13%
Lecturer 1 7%
Student > Ph. D. Student 1 7%
Unknown 11 73%
Readers by discipline Count As %
Medicine and Dentistry 3 20%
Biochemistry, Genetics and Molecular Biology 1 7%
Unknown 11 73%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 09 April 2024.
All research outputs
#15,759,273
of 24,953,268 outputs
Outputs from Journal of Neuroinflammation
#1,764
of 2,887 outputs
Outputs of similar age
#208,291
of 412,744 outputs
Outputs of similar age from Journal of Neuroinflammation
#42
of 67 outputs
Altmetric has tracked 24,953,268 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,887 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one is in the 35th percentile – i.e., 35% of its peers scored the same or lower than it.
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 412,744 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 67 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.