Selective COX-2 Inhibition Prevents Progressive Dopamine Neuron Degeneration in a Rat Model of Parkinson's Disease

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Selective COX-2 Inhibition Prevents Progressive Dopamine Neuron Degeneration in a Rat Model of Parkinson's Disease

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Title: Selective COX-2 Inhibition Prevents Progressive Dopamine Neuron Degeneration in a Rat Model of Parkinson's Disease
Author: Sánchez-Pernaute, Rosario; Ferree, Andrew; Yu, Meixiang; Cooper, Oliver Jamie; Brownell, Anna-Liisa; Isacson, Ole Stefan

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Citation: Sánchez-Pernaute, Rosario, Andrew Ferree, Oliver Cooper, Meixiang Yu, Anna-Liisa Brownell, and Ole Isacson. 2004. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. Journal of Neuroinflammation 1: 6.
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Abstract: Several lines of evidence point to a significant role of neuroinflammation in Parkinson's disease (PD) and other neurodegenerative disorders. In the present study we examined the protective effect of celecoxib, a selective inhibitor of the inducible form of cyclooxygenase (COX-2), on dopamine (DA) cell loss in a rat model of PD. We used the intrastriatal administration of 6-hydroxydopamine (6-OHDA) that induces a retrograde neuronal damage and death, which progresses over weeks. Animals were randomized to receive celecoxib (20 mg/kg/day) or vehicle starting 1 hour before the intrastriatal administration of 6-OHDA. Evaluation was performed in vivo using micro PET and selective radiotracers for DA terminals and microglia. Post mortem analysis included stereological quantification of tyrosine hydroxylase, astrocytes and microglia. 12 days after the 6-OHDA lesion there were no differences in DA cell or fiber loss between groups, although the microglial cell density and activation was markedly reduced in animals receiving celecoxib (p < 0.01). COX-2 inhibition did not reduce the typical astroglial response in the striatum at any stage. Between 12 and 21 days, there was a significant progression of DA cell loss in the vehicle group (from 40 to 65%) that was prevented by celecoxib. Therefore, inhibition of COX-2 by celecoxib appears to be able, either directly or through inhibition of microglia activation to prevent or slow down DA cell degeneration.
Published Version: doi://10.1186/1742-2094-1-6
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC483059/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8347349

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