Neuroprotective effects of celecoxib against degeneration of dopaminergic neurons induced by lipopolysaccharide

Objectives To explore the effect and possible mechanism of celecoxib on degeneration of dopaminergic neurons induced by intranigral injection of lipopolysaccharide(LPS).Methods Thirty female Sprague-Dawley rats were randomly divided into three groups:PBS group,physiologic saline +LPS group and celecoxib+LPS group.On d 14 after injection of LPS 15 μg or PBS,the number of tyrosine hydroxylase(TH)-positive neurons and the morphological changes of OX-42 positive microglias in the substantia nigra(SN) were observed by immunohistochemistry.COX-2 protein expression was examined by immunoblotting,prostaglandin E2(PGE2) and tumor necrosis factor α(TNF-α) contents were measured with radioimmunoassay.Results Compared with PBS control group,TH-positive neurons in the SN on the LPS-injected side reduced to 16% of the opposite side in saline treated group(P0.05),COX-2 protein expression and PGE2 and TNF-α contents in SN were upregulated.Compared with saline treated group,43% TH-positive neurons survived in celecoxib treated group,(P0.05) and celecoxib significantly lowered the levels of PGE2,TNF-α and the microglial activation.Conclusions COX-2 may be involved in LPS-induced dopaminergic neurous degeneration.Celecoxib inhibits microglial activation and the neurotoxic secretions,prevents the dopaminergic neuron degeneration and loss.