DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium

Abstract

The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

Quo Vadis Anesthesiologist? The Value Proposition of Future Anesthesiologists Lies in Preserving or Restoring Presurgical Health after Surgical Insult

“…For example, immune system activation resembles sterile inflammation, not a septic process [23][24][25][26][27][28]. Surgery involves significant tissue destruction, blood loss, alteration in microbiota with the possible leak of the inflammatory pathogen-associated molecular pattern (PAMP), and the induction of catabolism [26,[29][30][31][32][33][34][35][36]. Similar abnormalities are seen in other critical care illnesses, including traumatic brain injury, COVID-19, ARDS, stroke, and acute coronary syndrome.…”

“…The recovery trajectory depends on the inherited features of the patient and the nature and magnitude of the stressor (Figure 2). Even a single incident of anesthesia, surgery, or other critical grade insults may reverberate for months and even years [27,32,33,39,42]. These parameters are modifiable during the post-and perioperative It is becoming increasingly apparent that regaining preoperative homeostasis during the postsurgical period is impossible in some individuals [19,20].…”

Role of hypoxia-inducible factor in postoperative delirium of aged patients: A review

“…When monitoring rSO 2 in elderly patients following noncardiac abdominal surgery, cerebral desaturation (hypoxia) has been noted in more than 20% of instances as one of the independent risk factors for postoperative delirium. [4–6]…”

“…Several pathophysiological mechanisms may contribute to delirium onset, including neurotransmitter imbalance, systemic inflammatory response syndrome, and neuroinflammation, [1][2][3] altered brain metabolism, and impaired neuronal network connectivity. [4][5][6][7][8][9] There is currently no convincing evidence that any prophylactic measure prevents postoperative delirium because the mechanism of postoperative delirium is not clear.…”

“…When monitoring rSO 2 in elderly patients following noncardiac abdominal surgery, cerebral desaturation (hypoxia) has been noted in more than 20% of instances as one of the independent risk factors for postoperative delirium. [4][5][6] Hypoxia stimulates the expression of hypoxia-inducible factor-1 (HIF-1), which controls the hypoxic response. [10][11][12][13][14][15] HIF-1 may have a protective role in regulating neuron apoptosis in neonatal hypoxia-ischemia brain damage and may promote the repair and rebuilding process in the brain that was damaged by hypoxia and ischemia.…”