Abstract
Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1α, IL-1β, TNF-α), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-κB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients.
Highlights
Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, characterized by the impairment of memory, information processing ability, and mental flexibility
Our aim was to investigate whether inhibiting Receptor-interacting protein kinase 1 (RIPK1) by Nec-1 could limit neuroinflammation and attenuate postoperative cognitive deficits in D-Gal-induced aged mice
We showed that anesthesia and surgery induced a significant deficit in spatial memory acquisition and long term memory to execute simple low difficult task in D-Gal-induced aged mice
Summary
Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, characterized by the impairment of memory, information processing ability, and mental flexibility. Intracisternal anti-inflammation treatments could obviously inhibit neuroinflammation and prevented POCD (Barrientos et al, 2012; Ma et al, 2015; Li et al, 2017). These suggest that limiting neuroinflammation during perioperative period is a possible way to prevent or alleviate POCD. Due to the difficulty of intracisternal administration in patients with surgery, people had Inhibiting RIPK1 Alleviates POCD tried to limit perioperative neuroinflammation by systemic inflammatory factor neutralization with specific antibodies, and had detected efficacious inhibition of neuroinflammation and significant improvement of postoperative cognitive function (Terrando et al, 2010, 2016). New treatment of limiting perioperative neuroinflammation is still pressing for the prevention of POCD
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