title: Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.
abstract: Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity.
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Si
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurology, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China.
authors.forename: Shanchao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan 250014, PR China. Electronic address: qywangkun1981@sohu.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021, PR China. Electronic address: wangdwsd@126.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan 250012, PR China. Electronic address: yimingliusdql@yeah.net.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003839:Deoxyadenosines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D003839:Deoxyadenosines; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D062793:Occludin; C568987:Ocln protein, rat; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019255:NADPH Oxidases; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C058120:cordycepin
keywords: Anti-inflammatory; Anti-oxidative; Blood-brain barrier integrity; Cordycepin; Neuroprotective; Traumatic brain injury