Authors: Mei Cui Hongyan Ding Fangzhe Chen Yanxin Zhao Qi Yang Qiang Dong
Publish Date: 2014/11/27
Volume: 53, Issue: 1, Pages: 240-253
Abstract
This study aimed to examine whether the neuroprotective effects of Mdivi1 are attributable to extracellular ATP and adenosine Mdivi1 was administered prior to or post middle cerebral artery occlusion MCAO The extracellular adenosine was measured by in vivo microdialysis and highpressure liquid chromatography HPLC in MCAO mouse model Western blot was done to determine the influence of Mdivi1 on the expression of CD39 and CREB phosphorylation both in vivo and in the cultured astrocytes Intracellular cAMP and protein kinase A PKA activity were detected in primary astrocytes Results showed that Mdivi1 significantly reduced infarct volume and neurological scores when administered either prior to or post MCAO Interestingly pretreatment with Mdivi1 resulted in marked increase of extracellular adenosine and concomitant decrease in ATP The expression of CD39 but not CD73 was upregulated by Mdivi1 which was associated with the elevated phosphorylated cAMP response elementbinding protein CREB a transcription factor potentially regulating CD39 expression In primary astrocytes Mdivi1 treatment induced increases in intracellular cAMP PKA activity and CREB phosphorylation and PKAspecific inhibitor completely reversed Mdivi1induced CD39 expression Our results demonstrate that Mdivi1 protects against ischemic brain injury through increasing extracellular adenosine a process involving elevated CD39 expression that is likely modulated by cAMP/PKA/CREB cascadePotential mechanisms by which Mdivi1 mediates the neuroprotection on cerebral ischemic stroke Results from the present study indicate that Mdivi1 protects against ischemic brain injury through increasing extracellular adenosine a process involving elevated CD39 expression that is likely modulated by the cAMP/PKA/CREB cascades
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