title: Neuroprotective effect of breviscapine on traumatic brain injury in rats associated with the inhibition of GSK3β signaling pathway.
abstract: Breviscapine, a standardized Chinese herbal medicine extracted from Erigeron breviscapine, has been widely used to treat cerebrovascular diseases. However, there are no reports about the neuroprotective effects and underlying molecular mechanisms of breviscapine on traumatic brain injury (TBI). Therefore, this study was aimed to investigate the effects of breviscapine on rats with TBI insult and illuminate the underlying mechanism. We created a traumatic brain-injured model with breviscapine lateral ventricle injection and evaluated the expressional changes of glycogen synthase kinase 3 beta (GSK3β) as well as the GSK3β-involved signaling pathways including apoptosis and axonal growth. At 7, 14, 21days after injection, we found a great reduction of motor disability in TBI rats following breviscapine treatment, which was accompanied with a notably increased expression of phospho-Ser9-GSK3β (p-Ser9-GSK3β) and decreased expression of phosphor-Try216-GSK3β (p-Try216-GSK3β) at 7days after injection. Concomitantly, an enhanced expression of synaptic marker synaptophysin (SYP) together with a weakened expression of pro-apoptotic caspase3 was observed after TBI rats were treated with breviscapine. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) immunohistochemical assay and SYP immunofluorescence staining also confirmed the result. This study suggests that breviscapine inhibits the GSK3β signaling pathway to promote neurobehavioral function following neurotrauma. These events may provide a new insight into the mechanism of breviscapine treating brain injury.
authors.affiliation: Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China; Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming, Yunnan 650000, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Dong
authors.affiliation: Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China; Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming, Yunnan 650000, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Kun-Hua
authors.initials: KH
authors.lastname: Wang
authors.affiliation: Department of Experimental Zoology, Kunming Medical University, Kunming, Yunnan 650031, China. Electronic address: liujiaaixuexi@126.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China; Key Laboratory of National Physical Fitness and Altitude Training Adaptation in Yunnan Province, Institute of Physical Education, Yunnan Normal University, Kunming, Yunnan 650000, China; Department of Experimental Zoology, Kunming Medical University, Kunming, Yunnan 650031, China. Electronic address: tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016708:Synaptophysin; C569016:Syp protein, rat; C061097:breviscapine; D000071679:Glycogen Synthase Kinase 3 beta; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Apoptosis; Breviscapine; Glycogen synthase kinase 3 beta; Neuroprotection; Synapse growth; Traumatic brain injury