Anesthesia and surgery-induced elevation of CSF sTREM2 is associated with early cognitive dysfunction after thoracoabdominal aortic dissection surgery

Wang, Kexin; Cao, Xun; Li, Zhe; Liu, Sidan; Zhou, Yongjian; Guo, Lili; Li, Pengli

doi:10.1186/s12871-022-01955-4

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…ECS decrease due to isoflurane was also found using an MRI visible tracer in the study conducted by Zhao et al 19 Decreased ECS volume is known to reduce brain clearance. 5 Interestingly, it was found that the CSF tau/Aβ ratio was higher after surgery under isoflurane anesthesia than before anesthesia, 65,66 consistent with the reduced ECS and lower waste clearance rate under isoflurane. While we believe ECS shrinkage to be the main cause of our findings, multiple effects may contribute to our findings.…”

Section: Interpretation Of Resultsmentioning

confidence: 75%

Anesthesia‐related brain microstructure modulations detected by diffusion magnetic resonance imaging

Lindhardt,

Skoven,

Bordoni

et al. 2023

NMR in Biomedicine

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Recent studies have shown significant changes to brain microstructure during sleep and anesthesia. In vivo optical microscopy and magnetic resonance imaging (MRI) studies have attributed these changes to anesthesia and sleep‐related modulation of the brain's extracellular space (ECS). Isoflurane anesthesia is widely used in preclinical diffusion MRI (dMRI) and it is therefore important to investigate if the brain's microstructure is affected by anesthesia to an extent detectable with dMRI. Here, we employ diffusion kurtosis imaging (DKI) to assess brain microstructure in the awake and anesthetized mouse brain (n = 22). We find both mean diffusivity (MD) and mean kurtosis (MK) to be significantly decreased in the anesthetized mouse brain compared with the awake state (p < 0.001 for both). This effect is observed in both gray matter and white matter. To further investigate the time course of these changes we introduce a method for time‐resolved fast DKI. With this, we show the time course of the microstructural alterations in mice (n = 5) as they transition between states in an awake‐anesthesia‐awake paradigm. We find that the decrease in MD and MK occurs rapidly after delivery of gas isoflurane anesthesia and that values normalize only slowly when the animals return to the awake state. Finally, time‐resolved fast DKI is employed in an experimental mouse model of brain edema (n = 4), where cell swelling causes the ECS volume to decrease. Our results show that isoflurane affects DKI parameters and metrics of brain microstructure and point to isoflurane causing a reduction in the ECS volume. The demonstrated DKI methods are suitable for in‐bore perturbation studies, for example, for investigating microstructural modulations related to sleep/wake‐dependent functions of the glymphatic system. Importantly, our study shows an effect of isoflurane anesthesia on rodent brain microstructure that has broad relevance to preclinical dMRI.

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Section: Interpretation Of Resultsmentioning

confidence: 75%

Anesthesia‐related brain microstructure modulations detected by diffusion magnetic resonance imaging

Lindhardt,

Skoven,

Bordoni

et al. 2023

NMR in Biomedicine

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“…Only recently, Wang et al revealed that a higher value of postoperative sTREM2 in the CSF increased the risk of early POCD. These data were adjusted for POD duration [ 39 ]. It is likely that sTREM2-mediated microglial activation induces acute neuroinflammation.…”

Section: Discussionmentioning

confidence: 99%

Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery

Ruhnau,

Müller,

Nowak

et al. 2023

IJMS

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Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

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Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass

Zhuang

Xu²,

Zheng

et al. 2023

Ibrain

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Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes in the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) is a common central nervous system complication after cardiac surgery. The etiology and mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, and other factors are related to the pathogenesis of POCD. There is a close relationship between CPB and POCD, as CPB can cause inflammation, hypoxia and reperfusion injury, and microemboli formation, all of which can trigger POCD. POCD increases medical costs, seriously affects patients' quality of life, and increases mortality. Currently, there is a lack of effective treatment methods for POCD. Commonly used methods include preoperative health management, reducing inflammation response during surgery, preventing microemboli formation, and implementing individualized rehabilitation programs after surgery. Strengthening preventive measures can minimize the occurrence of POCD and its adverse effects.

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Anesthesia and surgery-induced elevation of CSF sTREM2 is associated with early cognitive dysfunction after thoracoabdominal aortic dissection surgery

Cited by 3 publications

References 57 publications

Anesthesia‐related brain microstructure modulations detected by diffusion magnetic resonance imaging

Anesthesia‐related brain microstructure modulations detected by diffusion magnetic resonance imaging

Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery

Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass

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