Neuroimmune synapse and modulation by anesthetics: Inflammatory mechanisms and therapeutic perspectives for postoperative neurocognitive disorders

Table 1 Summarize the research on the effects of some drugs and therapies on postoperative neurocognitive disorder

Drugs/therapies	Target	Pathway	Effect	Ref.
MCC950	NLRP3	NLRP3 inflammasome pathway	Reduce the expression of pro-inflammatory cytokines and relieve neuroinflammation	[132]
Atorvastatin	NLRP3	NLRP3 inflammasome pathway, NF-κB pathway	Play a neuroprotective role	[133]
IL-6 blocking therapy	IL-6		Reduce the expression of proinflammatory cytokine IL-6 and play a neuroprotective role	[88]
Maraviroc	CCR5/cAMP response element binding protein/NLRP1	CCR5/cAMP response element binding protein/NLRP1 pathway	Reduce neuroinflammation and improve cognitive impairment	[135]
Celastrol	Caspase-3/gasdermin E	cGAS-STING signaling pathway	Improving cognitive performance of POCD mice	[96]
Melatonin	Matrix metalloproteinase-9	Inflammatory pathway	Reduce neuroinflammation and synaptic dysfunction, improve delirium like behavior	[45]
Lactic acid	SIRT1	SIRT1 pathway	Improve POCD	[136]
Resveratrol	SIRT1	SIRT1 pathway, NF-κB pathway	Regulate microtubule function	[21]
Nrf2 activator	Nrf2		Inhibit neuroinflammation, promote neurogenesis, and improve cognitive function	[20,70]
Irisin	Microglia		Reprogramming microglia as anti-inflammatory M2 phenotype to prevent POCD	[19]
Galantamine	Cholinesterase	Cholinergic anti-inflammatory pathway	Restore the function of astrocytes and synapses	[137]
Varenicline	Tau protein		Reduce tau protein mislocalization, DNA damage and neuronal apoptosis, and improve cognition	[138]
Ginsenoside Rg1		Endocytosis lysosomal pathway	Eliminating β-amyloid and alleviating cognitive and synaptic deficits in elderly POCD mice	[139]
Probiotics	NLRP3	NLRP3 inflammasome pathway	Reduce the incidence of POCD in elderly patients. Reduce the incidence of POCD in elderly patients	[51,52]
Extracellular vesicles			Deliver therapeutic molecules to achieve precise treatment of central lesion area	[43,59]
Intranasal insulin	P3R/glucose-regulated protein 75/voltage-dependent anion channel 1	Phosphoinositide 3-kinases/protein kinase B signaling pathway	Reduce the level of proinflammatory cytokines and play a neuroprotective role	[76,142]
Coenzyme Q10	Mitochondria		Alleviate memory deficits	[143]
WS635	Mitochondria		Reduce synaptic damage and mitochondrial dysfunction	[144]
Elamipretide	NLRP3	NLRP3 inflammasome pathway	Restore damaged mitochondrial and synaptic functions	[145]
Lomastatin			Improve synaptic defects of neurons	[146,147]
Electroacupuncture		Multiple pathways	Neuroprotective effect	[71,150-152]
Vagus nerve stimulation	Acetylcholine	Cholinergic anti-inflammatory pathway	Exert anti-inflammatory effect	[57]
Preoperative and postoperative intervention		PPAR-gamma coactivator-1α/brain-derived neurotrophic factor pathway	Improving cognitive and inflammatory status in aged mice	[153]
Environmental enrichment			Reduce cognitive impairment and neuroinflammation caused by anesthesia/surgery	[155-157]

IL: Interleukin; Nrf2: Nuclear factor erythroid 2 related factor 2; NLRP: Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein; NF-κB: Nuclear factor-κB; cGAS: Cyclic GMP-AMP; STING: Stimulator of interferon genes; PPAR: Peroxisome proliferator-activated receptor; POCD: Postoperative cognitive dysfunction; SIRT1: Sirtuin 1; CCR5: C-C chemokine receptor type 5.