Quercetin has a neuroprotective role in focal cerebral ischemia. - GreenMedInfo Summary
The role of ASIC1a in neuroprotection elicited by quercetin in focal cerebral ischemia.
Brain Res. 2011 Jan 28. Epub 2011 Jan 28. PMID: 21281608
Division of Cyclotron&Radiopharmaceutical Sciences; Institute of Nuclear Medicine and Allied Sciences; Brig SK Mazumdar Road; Delhi; India-110054; School of Biomedical Engg.; Institute of Technology; Banaras Hindu University; Varanasi;India-221005.
One of the major instigators to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation. The intracellular calcium overload resulting from glutamate excitotoxicity is considered major determinant for neuronal loss during cerebral ischemia. Moreover, ASIC1a activation due to acidosis also promotes intracellular calcium overload during ischemic insult. Interestingly, ASIC1a was found to be inhibited by some flavonoids which carrying anti-inflammatory property particularly quercetin, which could be exploited in hypoxic conditions like cerebral ischemia. This encourages us to investigate neuroprotective effect of quercetin besides its possible downstream signaling mechanism in focal cerebral ischemia. The treatment of quercetin 30min before ischemia and 4h after reperfusion show significant protection from ischemic injury as noticeable by reduction in cerebral infarct volume and neurobehavioral deficit. In addition to earlier calcium dependent rise in the levels of nitrite and MDA exhibited marked reduction (P<0.01) in their levels when given quercetin pretreatment in ischemic brain regions. The quercetin treatment also reduced the spectrin break down products (SBDP) caused by ischemic activation of calcium dependent protease calpain. In ex-vivo study, it was also observed that quercetin inhibited the acid mediated intracellular calcium levels in rat brain synaptoneurosomes. These studies suggest that neuroprotective role of quercetin in focal cerebral ischemia by regulation of ASIC1a.