title: Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.
abstract: Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption.
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Su
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China. Electronic address: lxm5668sw@yahoo.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Neurology, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, China. Electronic address: liangguobiao6708@163.com.
authors.forename: Guobiao
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D020208:Brain Injury, Chronic / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D008297:Male; D016328:NF-kappa B / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D062725:Tight Junction Proteins / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D062725:Tight Junction Proteins; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D047310:Apigenin
keywords: Apigenin; Early brain injury; Inflammation; Neuroprotective effect; Subarachnoid hemorrhage; Tight junction proteins