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Delayed Administration of Parecoxib, a Specific COX-2 Inhibitor, Attenuated Postischemic Neuronal Apoptosis by Phosphorylation Akt and GSK-3β

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Abstract

Parecoxib is a recently described novel COX-2 inhibitor whose functional significance and neuroprotective mechanisms remain elusive. Therefore, in this study, we aimed to investigate whether delayed administration of parecoxib inhibited mitochondria-mediated neuronal apoptosis induced by ischemic reperfusion injury via phosphorylating Akt and its downstream target protein, glycogen synthase kinase 3β (GSK-3β). Adult male Sprague–Dawley rats were administered parecoxib (10 or 30 mg kg−1, IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and the protein expression of p-Akt, p-GSK-3β and Cytochrome C in cerebral ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly diminished infarct volume and attenuated neuron apoptosis in a dose-independent manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3β was observed in the ischemic penumbra of parecoxib group after stroke. Moreover, parecoxib also reduced the release of Cytochrome C from mitochondrial into cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken together, these results suggested that parecoxib ameliorated postischemic mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in rats and this neuroprotective potential is involved in phosphorylation of Akt and GSK-3β.

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Abbreviations

COX-2:

Cyclooxygenase-2

GSK-3β:

Glycogen synthase kinase 3β

MCAO:

Middle cerebral artery occlusion

PI3 K:

Phosphatidylinositol-3 kinase

NSAIDS:

Non-steroidal anti-inflammatory drugs

TTC:

2, 3, 5-triphenyl-tetrazolium chloride

BBB:

Blood brain barrier

ADC:

Apparent diffusion coefficient

ANT:

Adenine nucleotide translocase

MPTP:

Mitochondrial permeability transition pore

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Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Xiangya Hospital of Center South University, Changsha, 410078, Hunan Province, China

    Zhi Ye, Na Wang, Pingping Xia, E. Wang, Yajing Yuan & Qulian Guo

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  1. Zhi Ye
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Correspondence to Qulian Guo.

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Ye, Z., Wang, N., Xia, P. et al. Delayed Administration of Parecoxib, a Specific COX-2 Inhibitor, Attenuated Postischemic Neuronal Apoptosis by Phosphorylation Akt and GSK-3β. Neurochem Res 37, 321–329 (2012). https://doi.org/10.1007/s11064-011-0615-y

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  • DOI: https://doi.org/10.1007/s11064-011-0615-y

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