RT Journal Article
SR Electronic
T1 Neuroprotective effects of all-trans-retinoic acid are mediated via downregulation of TLR4/NF-κB signaling in a rat model of middle cerebral artery occlusion
JF Neurosciences Journal
JO Neurosciences (Riyadh)
FD Prince Sultan Military Medical City
SP 276
OP 283
DO 10.17712/nsj.2024.4.20240010
VO 29
IS 4
A1 Tan, Lixi
A1 Liu, Qian
A1 Chen, Songfa
A1 You, Rongjiao
A1 Li, Xinyue
A1 Wen, Tao
A1 Peng, Zhongxing
YR 2024
UL http://nsj.org.sa/content/29/4/276.abstract
AB Objectives: To determine the effects of all-trans-retinoic acid (ATRA) on the post-stroke inflammatory response and elucidate the underlying molecular mechanisms.Methods: This animal experiment was conducted at Central Laboratory, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China during 2020-2022. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h, and treated with ATRA at 2 and 24 h after reperfusion. Neurological deficit scores on behavioral tests, and cerebral infarct volume, microglial polarization, and the expression levels of inflammatory cytokines and proteins associated with TLR4/NF-κB signaling were assessed.Results: The ATRA administration reduced cerebral infarct volume and ameliorated neurological deficit scores in MCAO rats. Additionally, ATRA relieved cerebral edema and downregulated the secretion of proinflammatory cytokines after stroke. Finally, ATRA attenuated the polarization of the microglia toward the M1 phenotype and promoted the activation of the beneficial M2 phenotype; the underlying mechanism potentially involved the suppression of the TLR4/NF-κB signaling pathway.Conclusion: The ATRA treatment promoted functional recovery in an experimental model of ischemic stroke by attenuating neural inflammation. ATRA potentially modulated microglia-mediated neuroinflammation via the downregulation of the TLR4/NF-κB signaling pathway, which makes it a candidate treatment for post-stroke neuroinflammation.