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A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Fast green FCF prevents postoperative cognitive dysfunction via the downregulation of the P2X4 receptor in mice
1The First Affiliated Hospital of Ningbo University, Ningbo 315010, China.
Abstract:
Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10-12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor-κB (NF-κB), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD.
Insights
Fast green FCF (FGF), a food dye, may prevent postoperative cognitive dysfunction (POCD) by reducing P2X4 receptor expression in the brain. This study shows FGF alleviates cognitive decline and neuroinflammation in mice, suggesting potential therapeutic use.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) is a significant concern in aged patients, with unclear pathological mechanisms.
- Overexpression of the P2X4 receptor in the central nervous system (CNS) is linked to POCD onset.
Purpose of the Study:
- To investigate if Fast green FCF (FGF) can prevent POCD by down-regulating CNS P2X4 receptor expression.
- To explore the therapeutic potential of FGF for POCD.
Main Methods:
- An animal model of POCD was established in mice using exploratory laparotomy under anesthesia.
- FGF's effects on cognitive function, P2X4 receptor expression, microglial polarization, NF-κB phosphorylation, and pro-inflammatory cytokines were assessed.
- The role of the P2X4 receptor was further examined using a specific antagonist (5-BDBD) and an allosteric modulator (ivermectin).
Main Results:
- FGF significantly attenuated surgical-induced cognitive impairments and reduced P2X4 receptor expression in mice.
- Blocking the P2X4 receptor with 5-BDBD demonstrated cognitive-enhancing effects in POCD mice.
- FGF's effects were reversed by ivermectin, confirming P2X4 receptor involvement.
- FGF inhibited M1 microglial polarization, decreased NF-κB phosphorylation, and reduced pro-inflammatory cytokine production.
Conclusions:
- FGF exhibits anti-POCD effects by down-regulating P2X4 receptor-associated neuroinflammation.
- These findings suggest FGF holds promise as a potential therapeutic agent for preventing POCD.
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