Evidence for the role of phosphatidylcholine-specific phospholipase in experimental subarachnoid hemorrhage in rats.
Neuron apoptosis and inflammatory responses contribute to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI), which is the main aspect that affects patients' outcome. Previous research has demonstrated that phosphatidylcholine-specific phospholipase C (PC-PLC) plays critical roles in cell apoptosis and various inflammatory responses, and that tricyclodecan-9-yl-xanthogenate (D609), a well known PC-PLC inhibitor, is a powerful agent to protect brain from cerebral ischemic injury and SAH-induced cerebral vasospasm. However, the association between PC-PLC and SAH-induced EBI is undetermined. Therefore, we sought to investigate whether PC-PLC was implicated in SAH-induced EBI. Compared with sham group, an upregulation of PC-PLC activity was detected in the brain tissue and serum of SAH group. Pharmacological blockade of PC-PLC by D609 attenuated neurological behavior impairment, brain edema and blood-brain barrier (BBB) damage induced by SAH. In addition, D609 treatment significantly inhibited SAH-induced inflammatory response and neuron apoptosis. Furthermore, inhibition of PC-PLC in primary-cultured rat cortical neurons attenuated oxyhemoglobin (OxyHb)-induced apoptosis morphology and decrease in survival rate. In conclusion, our data suggest that PC-PLC participates in SAH-induced EBI.
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Bo
B
Li
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Haiying
H
Li
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Zhong
Z
Wang
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Yang
Y
Wang
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Anju
A
Gao
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Yonghua
Y
Cui
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Yizhi
Y
Liu
Department of Neurosurgery and Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. Electronic address: nju_neurosurgery@163.com.
Gang
G
Chen
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D001929:Brain Edema / Q000209:etiology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009636:Norbornanes; D010108:Oxyhemoglobins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D013859:Thiocarbamates; D013871:Thiones / Q000627:therapeutic use; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D000975:Antioxidants; D001952:Bridged-Ring Compounds; D009636:Norbornanes; D010108:Oxyhemoglobins; D013859:Thiocarbamates; D013871:Thiones; D014841:von Willebrand Factor; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; D010751:Phosphopyruvate Hydratase
Early brain injury; Phosphatidylcholine-specific phospholipase C; Subarachnoid hemorrhage; Tricyclodecan-9-yl-xanthogenate