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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Cardiopulmonary Resuscitation | Research

Flufenamic acid improves survival and neurologic outcome after successful cardiopulmonary resuscitation in mice

Authors: Jiancong Chen, Yuan Chang, Juan Zhu, Yuqin Peng, Zheqi Li, Kunxue Zhang, Yuzhen Zhang, Chuman Lin, Zhenzhou Lin, Suyue Pan, Kaibin Huang

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Brain injury is the main cause of high mortality and disability after successful cardiopulmonary resuscitation (CPR) from sudden cardiac arrest (CA). The transient receptor potential M4 (TRPM4) channel is a novel target for ameliorating blood–brain barrier (BBB) disruption and neuroinflammation. Herein, we tested whether flufenamic acid (FFA), which is reported to block TRPM4 with high potency, could confer neuroprotection against brain injury secondary to CA/CPR and whether its action was exerted by blocking the TRPM4 channel.

Methods

Wild-type (WT) and Trpm4 knockout (Trpm4−/−) mice subjected to 10-min CA/CPR were randomized to receive FFA or vehicle once daily. Post-CA/CPR brain injuries including neurologic deficits, survival rate, histological damage, edema formation, BBB destabilization and neuroinflammation were assessed.

Results

In WT mice subjected to CA/CPR, FFA was effective in improving survival and neurologic outcome, reducing neuropathological injuries, attenuating brain edema, lessening the leakage of IgG and Evans blue dye, restoring tight junction protein expression and promoting microglia/macrophages from the pro-inflammatory subtype toward the anti-inflammatory subtype. In comparison to WT mice, Trpm4−/− mice exhibited less neurologic deficiency, milder histological impairment, more BBB integrity and more anti-inflammatory microglia/macrophage polarization. As expected, FFA did not provide a benefit of superposition compared with vehicle in the Trpm4−/− mice after CA/CPR.

Conclusions

FFA mitigates BBB breach and modifies the functional status of microglia/macrophages, thereby improving survival and neurologic deficits following CA/CPR. The neuroprotective effects occur at least partially by interfering with the TRPM4 channel in the neurovascular unit. These results indicate the significant clinical potential of FFA to improve the prognosis for CA victims who are successfully resuscitated.
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Metadata
Title
Flufenamic acid improves survival and neurologic outcome after successful cardiopulmonary resuscitation in mice
Authors
Jiancong Chen
Yuan Chang
Juan Zhu
Yuqin Peng
Zheqi Li
Kunxue Zhang
Yuzhen Zhang
Chuman Lin
Zhenzhou Lin
Suyue Pan
Kaibin Huang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02571-2

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