Neuroprotective Effect of Flurbiprofen in Focal Cerebral Ischemia: The Possible Role of ASIC1a
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Mishra, Vikas
Verma, R K Raghubir, Ram |
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| Date |
2011-03-30T09:51:11Z
2011-03-30T09:51:11Z 2010 |
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| Identifier |
Neuropharmacology, 59 (7-8), 582-588
http://hdl.handle.net/123456789/662 |
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| Description |
The intracellular calcium overload resulting from glutamate excitotoxicity is considered major determinant for neuronal loss during cerebral ischemia. Moreover, acidosis mediated ASIC1a activation has also shown to promote intracellular calcium overload following ischemic insult. Interestingly, ASIC1a was found to be inhibited by NSAIDs particularly flurbiprofen and ibuprofen, which could be exploited in hypoxic conditions like cerebral ischemia. This prompted us to investigate neuroprotective effect of flurbiprofen, besides its possible downstream signaling mechanism in rodent model of focal cerebral ischemia.
The flurbiprofen treatment, thirty minutes prior to ischemia and four hour post- reperfusion, afforded significant neuroprotection from ischemic injury as evidenced by reduction in cerebral infarct volume and neurobehavioral deficit. Further, an early calcium dependant rise in levels of nitrite and MDA was also found to be significantly (P<0.01) reduced in ischemic brain regions following flurbiprofen pretreatment. It also reduced the proteolytic products (SBDPs) caused by ischemic activation of calcium dependant protease calpain. In addition, the ex-vivo studies with flurbiprofen in rat brain synaptoneurosomes inhibited the acid mediated rise in intracellular calcium levels. These studies thus provide neuroprotective profile of flurbiprofen in focal cerebral ischemia with its selective effect on ASIC1a.
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663049 bytes
application/pdf |
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| Language |
en
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| Relation |
CDRI Communication No 7959
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| Subject |
ASIC1
Flurbiprofen treatment |
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| Title |
Neuroprotective Effect of Flurbiprofen in Focal Cerebral Ischemia: The Possible Role of ASIC1a
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| Type |
Article
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