Zhongcong Xie
University of Texas Health Science Center at Houston, TX·Neuroscience
Older adults who have surgery under general anesthesia often develop confusion or memory and thinking problems afterward. These perioperative neurocognitive disorders (PND) include postoperative delirium (POD), a sudden state of confusion, as well as slower or lasting cognitive decline.
- Fields
Neuroscience
Medicine & Clinical Research
Pharmacology
- Topics
perioperative neurocognitive disorders
postoperative delirium
postoperative cognitive dysfunction
- Grants
- 4 known grants, through Apr 2031
What they work on
- Determine whether blood pTau217 (Tau phosphorylated at threonine 217) can be generated outside the brain and is driven by gut microbiota and their metabolites IPA and butyric acid, in 400 older adults having orthopedic surgery, using Simoa assays and brain-specific Tau antibodies.
- Test whether pre- and postoperative non-brain pTau217, gut microbiota profiles, IPA and butyric acid predict postoperative delirium and cognitive decline and strengthen the link between IL-6/CRP inflammation and these disorders.
- Assess how anesthesia/surgery changes Tau, pTau and cyclophilin D (CypD, a mitochondrial protein) in blood monocytes, and how this relates to neuroinflammation and cognition in adult, aged and AD transgenic mice, using two-photon imaging and electrophysiology.
- Test whether the pTau–CypD interaction in monocytes is required for postoperative cognitive problems using Tau and CypD knockout chimeric mice, and whether blocking the NF-κB–NLRP3 inflammasome cascade reduces them.
- Determine whether the lower bond-dissociation energy of isoflurane and sevoflurane, compared with desflurane, explains why they activate GSK3β (the enzyme that phosphorylates Tau) and impair cognition, in male and female aged and 5XFAD mice.
- Test whether testosterone and estradiol bind phosphorylated GSK3β to block anesthetic-induced Tau phosphorylation, using estrogen and androgen receptor knockout mice to establish cause and effect.
- Evaluate whether abdominal surgery under anesthesia causes delirium-like behavior in aged and AD mice through IL-6 neuroinflammation and brain pTau, measured with a mouse Confusion Assessment Method and nanobeam biosensing.
- Determine how pTau and IL-6 pass between cultured neurons and microglia from IL-6 and Tau knockout mice, and test whether naproxen, parecoxib or lithium prevent delirium-like behavior.
More about the research
They raise the risk of complications and death, increase costs, and are linked to a higher risk of Alzheimer's disease (AD) and related dementias. Their causes remain largely unknown. Across four projects, the lab studies how anesthesia and surgery may act on Tau, a brain protein that becomes chemically altered (phosphorylated, pTau) in AD, and on inflammation. The work spans patients, mice and cultured cells.
Why it matters
Delirium and cognitive decline after surgery are common in older patients and are linked to Alzheimer's disease and related dementias. This work could provide blood and gut-microbiome biomarkers to identify at-risk patients before surgery. It may also point to anesthetic choices suited to women versus men, and suggest treatment targets such as GSK3β, CypD or inflammation. Together these could lead to safer anesthesia and surgical care for older adults and people with AD.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Charles Brown
Stanford University, CA·Medicine & Clinical Research
Test whether cerebrospinal fluid markers of blood-brain barrier leak, inflammation, and neuron and astrocyte injury — including the CSF/blood albumin ratio, cytokines, neurofilament light and glial fibrillary acidic protein — are associated with delirium after aortic surgery in 180 patients with CSF drains.
Guang Yang
Columbia University, NY·Neuroscience
Test whether glutamate-releasing inputs from the ventral tegmental area (VTA) to the prefrontal cortex weaken after peripheral nerve injury and drive chronic pain, using in vivo calcium imaging and cell type- and projection-specific chemogenetics in mice.
Giuseppe Faraco
Weill Medical College of Cornell University, NY·Neuroscience
Test whether colonizing the mouse small intestine with segmented filamentous bacteria expands gut Th17 immune cells, raises blood IL17, and impairs brain blood vessel function and cognition in male, female and aging mice.
The school
University of Texas Health Science Center at Houston: 25 labs on PI Pages, $419M a year on research, 340 research doctorates a year.
More about University of Texas Health Science Center at Houston
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