TY - JOUR
T1 - Protective effects of Ephedra sinica extract on blood-brain barrier integrity and neurological function correlate with complement C3 reduction after subarachnoid hemorrhage in rats
AU - Zuo, Shilun
AU - Li, Wenyan
AU - Li, Qiang
AU - Zhao, Hengli
AU - Tang, Jun
AU - Chen, Qianwei
AU - Liu, Xin
AU - Zhang, John H.
AU - Chen, Yujie
AU - Feng, Hua
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/11/16
Y1 - 2015/11/16
N2 - Early brain injury, which is associated with brain cell death, blood-brain barrier disruption, brain edema, and other pathophysiological events, is thought to be the main target in the prevention of poor outcomes after subarachnoid hemorrhage (SAH). Emerging evidences indicates that complement system, especially complement C3 is detrimental to neurological outcomes of SAH patients. Recently, Ephedra sinica extract was extracted and purified, which exhibits ability to block the activity of the classical and alternative pathways of complement, and improve neurological outcomes after spinal cord injury and ischemic brain injury. However, it is still unclear whether Ephedra sinica extract could attenuate early brain injury after SAH. In the present study, a standard endovascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. Ephedra sinica extract (15. mg/kg) was orally administrated daily and evaluated for effects on modified Garcia score, brain water content, Evans blue extravasation and fluorescence, cortex cell death by TUNEL staining, and the expressions of complement C3/C3b, activated C3, sonic hedgehog, osteopontin and matrix metalloproteinase-9 by western bolt and immunofluorescence staining. We founded that the Ephedra sinica extract alleviated the blood-brain barrier disruption and brain edema, eventually improved neurological functions after SAH in rats. These neuroprotective effects was associated with the inhibition of complement C3, possibly via upregulating sonic hedgehog and osteopontin signal, and reducing the expressions of matrix metalloproteinase-9. Taking together, these observations suggested complement C3 inhibition by the Ephedra sinica extract may be a protective factor against early brain injury after SAH.
AB - Early brain injury, which is associated with brain cell death, blood-brain barrier disruption, brain edema, and other pathophysiological events, is thought to be the main target in the prevention of poor outcomes after subarachnoid hemorrhage (SAH). Emerging evidences indicates that complement system, especially complement C3 is detrimental to neurological outcomes of SAH patients. Recently, Ephedra sinica extract was extracted and purified, which exhibits ability to block the activity of the classical and alternative pathways of complement, and improve neurological outcomes after spinal cord injury and ischemic brain injury. However, it is still unclear whether Ephedra sinica extract could attenuate early brain injury after SAH. In the present study, a standard endovascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. Ephedra sinica extract (15. mg/kg) was orally administrated daily and evaluated for effects on modified Garcia score, brain water content, Evans blue extravasation and fluorescence, cortex cell death by TUNEL staining, and the expressions of complement C3/C3b, activated C3, sonic hedgehog, osteopontin and matrix metalloproteinase-9 by western bolt and immunofluorescence staining. We founded that the Ephedra sinica extract alleviated the blood-brain barrier disruption and brain edema, eventually improved neurological functions after SAH in rats. These neuroprotective effects was associated with the inhibition of complement C3, possibly via upregulating sonic hedgehog and osteopontin signal, and reducing the expressions of matrix metalloproteinase-9. Taking together, these observations suggested complement C3 inhibition by the Ephedra sinica extract may be a protective factor against early brain injury after SAH.
KW - Blood-brain barrier
KW - Complement C3
KW - Early brain injury
KW - Ephedra sinica
KW - Subarachnoid hemorrhage
KW - Matrix Metalloproteinase 9/metabolism
KW - Hedgehog Proteins/metabolism
KW - Male
KW - Brain Edema/drug therapy
KW - Permeability
KW - Neuroprotective Agents/pharmacology
KW - Rats, Sprague-Dawley
KW - Osteopontin/metabolism
KW - Animals
KW - Blood-Brain Barrier/drug effects
KW - Complement C3/metabolism
KW - Ephedra sinica/chemistry
KW - Cell Death
KW - Cerebral Cortex/drug effects
KW - Plant Extracts/pharmacology
KW - Subarachnoid Hemorrhage/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=84945565195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945565195&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/b14d1ea9-af45-3de3-b5c3-5e55d4a86e6d/
U2 - 10.1016/j.neulet.2015.10.056
DO - 10.1016/j.neulet.2015.10.056
M3 - Article
C2 - 26518242
SN - 0304-3940
VL - 609
SP - 216
EP - 222
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -