Details

Autor(en) / Beteiligte

• Tatenhorst, Lars
• Tönges, Lars
• Saal, Kim-Ann
• Koch, Jan C
• Szegő, Éva M
• Bähr, Mathias
• Lingor, Paul

Titel

Rho Kinase Inhibition by Fasudil in the Striatal 6-Hydroxydopamine Lesion Mouse Model of Parkinson Disease

Ist Teil von

• Journal of neuropathology and experimental neurology, 2014-08, Vol.73 (8), p.770-779

Ort / Verlag

England: by American Association of Neuropathologists, Inc

Erscheinungsjahr

2014

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• ABSTRACTChronic degeneration of nigrostriatal projections, followed by nigral dopaminergic cell death, is a key feature of Parkinson disease (PD). This study examines the neuroprotective potential of the rho kinase inhibitor fasudil in the 6-hydroxydopamine (6-OHDA) mouse model of PD in vivo. C57Bl/6 mice were lesioned by striatal stereotactic injections with 4 μg of 6-OHDA and treated with fasudil 30 or 100 mg/kg body weight via drinking water. Motor behavior was tested biweekly; histologic and biochemical analyses were performed at 4 and 12 weeks after lesion. Motor behavior was severely impaired after 6-OHDA lesion and was not improved by fasudil treatment. Fasudil 100 mg/kg did not significantly increase the number of dopaminergic cells in the substantia nigra after 12 weeks versus lesion controls. Interestingly, however, high-performance liquid chromatography analysis of dopamine metabolites revealed that striatal levels of 3,4-dihydroxyphenylacetic acid were significantly increased after 12 weeks, suggesting a regenerative response. In contrast to recent findings in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin model, fasudil effects seem limited in this severe 6-OHDA model of PD. Nevertheless, high therapeutic concentrations of fasudil are suggestive of a proregenerative potential for dopaminergic neurons, making further evaluations of rho kinase inhibition as a proregenerative therapeutic strategy in PD promising.