Quercetin alleviates microglial-induced inflammation after traumatic brain injury via the PGC-1α/Nrf2 pathway dependent on HDAC3 inhibition

• Published in: Brain research bulletin Vol. 217; p. 111080
• Main Authors: Zhai, Xiaofu, Wang, Ziyu, Gao, Juemin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2024; Elsevier
• Subjects: Animals; Apoptosis - drug effects; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - pathology; Disease Models, Animal; HDAC3; Histone Deacetylases - metabolism; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Male; Mice; Mice, Inbred C57BL; Microglia - drug effects; Microglia - metabolism; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; NF-E2-Related Factor 2 - metabolism; Nrf2; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; PGC-1α; Quercetin; Quercetin - pharmacology; Signal Transduction - drug effects; Traumatic brain injury; Inflammation; PGC-1α; Traumatic brain injury; HDAC3; Nrf2; Quercetin
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2024.111080

Inflammation and neuronal apoptosis play a key role in traumatic brain injury (TBI). Quercetin (Que) has been shown to exhibit a neuroprotective effect after TBI, but the underlying molecular mechanism remains unclear. In this study, We established a weight-drop mouse model to illustrate the effects of Que on microglial-induced inflammation in TBI. Mice were divided into four groups: the Sham group, TBI group, TBI+vehicle group, and TBI+Que group. The TBI+Que group was treated with Que 30 min after TBI. Brain water content, neurological score, and neuronal apoptosis were measured. Western blotting, TUNEL staining, Nissl staining, quantitative polymerase chain reaction, and immunofluorescence staining were performed to assess the activation of the PGC-1α/Nrf2 pathway and nuclear translocation of HDAC3 with Que treatment. The results showed that Que administration alleviated TBI-induced neurobehavioral deficits, encephaledema, and neuron apoptosis. Que also restrained TBI-induced microglial activity and the subsequent expression of the inflammatory factor in the contusion cortex. Moreover, Que treatment activated the PGC-1α/Nrf2 pathway, attributable to the inhibition of HDAC3 translocation to the nucleus. Overall, these results reveal the role of Que in protecting against TBI-induced neuroinflammation and promoting neurological functional recovery, which is achieved through the negative regulation of HDAC3. •Blood Brain Barrier dysfunction, inflammation, microglial mediated release of proinflammatory mediators play key role in the pathogenesis of TBI.•Recent advancements on drug targets useful to prevent TBI induced neuronal insult.•Que promoted translocation of PGC-1α/Nrf2 pathway and provided neuroprotective effect.•Que inhibited HDAC3 to suppress microglial activation and mitigate neuro-inflammation.