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Journal of Neuroinflammation

, 1:6

First Online: 17 May 2004Received: 01 April 2004Accepted: 17 May 2004

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.

List of abbreviations6-OHDA6-hydroxydopamine

ANOVAanalysis of variance

BPbinding potential

CFT2β-carbomethoxy-3β-4-fluorophenyl tropane

COXcyclooxygenase

COX-2cyclooxygenase type 2 isoform

COXIBCOX inhibitor

DAdopamine

DATdopamine transporters

DMSOdimethyl sulfoxide

GFAPglial fibrillary acidic protein

HClhydrogen chloride

HPLChigh performance liquid chromatography

IL-1βinterleukin-1 beta

LPSlipopolysaccharide

MAPKmitogen-activated protein kinase

MPTPN-methyl 1,2,3,6 tetrahydropyridine

NGSnormal goat serum

NOnitric oxide

NSAIDnonsteroidal anti-inflammatory drugs

OX42CD11b

PBSphosphate buffered saline

PDParkinson-s disease

PETpositron emission tomography

PK-11195N-sec-butyl-1-2-chlorophenyl-N-methylisoquinoline-3-carboxamide

ROSreactive oxygen species

SNsubstantia nigra

THtyrosine hydroxylase

TNFαtumor necrosis factor alpha

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-1-6 contains supplementary material, which is available to authorized users.

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Autor: Rosario Sánchez-Pernaute - Andrew Ferree - Oliver Cooper - Meixiang Yu - Anna-Liisa Brownell - Ole Isacson

Fuente: https://link.springer.com/



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