The possible neuroprotective role of a novel and highly selective cyclooxygenase-2 inhibitor GW637185X was studied in a model of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of nigrostriatal dopaminergic (DA) neurons in the mouse. Stereological and microdensitometrical analysis of nigral tyrosine hydroxylase-immunoreactive cell bodies and striatal tyrosine hydroxylase-immunoreactive terminals, respectively, showed that GW637185X exerted a full protection against MPTP-induced degeneration of the nigro-striatal pathway. In contrast to earlier studies, these findings demonstrate that acute inhibition of cyclooxygenase-2 can result in a full neuroprotective effect not only on nigral DA cell bodies, but also on striatal DA terminals in the mouse MPTP model.
The novel cyclooxygenase-2 inhibitor GW637185X protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity / J. A., Aguirre; Leo, Giuseppina; R., Cueto; B., Andbjer; A., Naylor; A. D., Medhurst; Agnati, Luigi Francesco; Fuxe, K.. - In: NEUROREPORT. - ISSN 0959-4965. - STAMPA. - 19:6(2008), pp. 657-660. [10.1097/WNR.0b013e3282fb7898]
The novel cyclooxygenase-2 inhibitor GW637185X protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity
LEO, Giuseppina;AGNATI, Luigi Francesco;
2008
Abstract
The possible neuroprotective role of a novel and highly selective cyclooxygenase-2 inhibitor GW637185X was studied in a model of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced injury of nigrostriatal dopaminergic (DA) neurons in the mouse. Stereological and microdensitometrical analysis of nigral tyrosine hydroxylase-immunoreactive cell bodies and striatal tyrosine hydroxylase-immunoreactive terminals, respectively, showed that GW637185X exerted a full protection against MPTP-induced degeneration of the nigro-striatal pathway. In contrast to earlier studies, these findings demonstrate that acute inhibition of cyclooxygenase-2 can result in a full neuroprotective effect not only on nigral DA cell bodies, but also on striatal DA terminals in the mouse MPTP model.
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