期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 43, 期 1, 页码 41-52出版社
WILEY
DOI: 10.1111/ejn.13132
关键词
fasudil; intranasal; LPS; mouse models; Parkinson's disease; ROCK
资金
- National Foundation of Natural Science of China [81070956, 81371414, 81272163, 81501085]
Microglia activation and inflammatory factors in brain microenvironment are associated with degeneration of neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients and various PD models. There is increasing evidence that the Rho/ROCK (Rho kinase) signalling pathway may play a critical role in the inflammatory response, and ROCK inhibitor has been reported to have neuroprotective effects. In this study, we examined the neuroprotective potential and possible mechanism of ROCK inhibitor Fasudil in an intranasal lipopolysaccharide (LPS)-induced PD model. ROCK was activated with LPS stimulation and inhibited by Fasudil treatment in this PD model. Behavioural tests demonstrated a clear improvement in motor performance after Fasudil treatment. Furthermore, Fasudil resulted in a significant attenuation of dopamine cell loss, alpha-synuclein accumulation and inflammatory response with the reversion of inflammatory M1 to anti-inflammatory M2 microglia, decreased NF-kappa B activation, and IL-12 and TNF-alpha generation in the SN and olfactory bulb in this model. This study establishes a role for Fasudil in protecting against LPS-mediated dopamine degeneration and provides a therapeutic strategy for the treatment of PD.
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