Evidence for the role of phosphatidylcholine-specific phospholipase in experimental subarachnoid hemorrhage in rats

Experimental Neurology
Bo LiGang Chen

Abstract

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 con...Continue Reading

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