Research Paper Volume 13, Issue 6 pp 8720—8736

Parvalbumin interneuron-mediated neural disruption in an animal model of postintensive care syndrome: prevention by fluoxetine

Yong Wang1, , Xiao-yu Yin2, , Xue He3, , Chen-mao Zhou1, , Jin-chun Shen2, , Jian-hua Tong3, ,

  • 1 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 2 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
  • 3 Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China

Received: June 19, 2020       Accepted: February 8, 2021       Published: February 22, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Postintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health, and physical function after critical illness and persisting beyond hospitalization, which is associated with reduced quality of life and increased mortality. Recently, we have developed a clinically relevant animal model of PICS based on two-hit hypothesis. However, the underlying mechanism remains unclear. Accumulating evidence has demonstrated that hippocampal GABAergic interneuron dysfunction is implicated in various mood disorders induced by stress. Thus, this study investigated the role of hippocampal GABAergic interneurons and relevant neural activities in an animal model of PICS. In addition, we tested whether fluoxetine treatment early following combined stress can prevent these anatomical and behavioral pathologies. In the present study, we confirmed our previous study that this PICS model displayed reproducible anxiety- and depression like behavior and cognitive impairments, which resembles clinical features of human PICS. This behavioral state is accompanied by hippocampal neuroinflammation, reduced parvalbumin (PV) expression, and decreased theta and gamma power. Importantly, chronic fluoxetine treatment reversed most of these abnormities. In summary, our study provides additional evidence that PV interneuron-mediated hippocampal network activity disruption might play a key role in the pathology of PICS, while fluoxetine offers protection via modulation of the hippocampal PV interneuron and relevant network activities.


GFAP: glial fibrillary acidic protein; LFP: For local field potential; LPS: lipopolysaccharide; MSD: meso scale discovery; IBA1: ionized calcium binding adapter molecule 1; ICU: intensive care unit; NOR: novel object recognition; PV: parvalbumin; PFA: paraformaldehyde; PBS: phosphate-buffered saline; PICS: Postintensive care syndrome; S.E.M.: standard error of the mean.