title: Riluzole improves motor deficits and attenuates loss of striatal neurons in a sequential double lesion rat model of striatonigral degeneration (parkinson variant of multiple system atrophy).
abstract: We investigated neuroprotective effects of riluzole, an anti-glutamatergic agent that is FDA approved for disease-modifying therapy in amyotrophic lateral sclerosis (ALS), in an established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with MSA (MSA-P). Riluzole was administered prior to and consecutively for ten days following double lesion placement in the left-sided medial forebrain bundle and ipsilateral striatum. Assessment of motor behaviour using a flex field system showed a significant reduction of motor disturbance in animals with striatonigral lesions treated with riluzole compared to lesioned but untreated animals (P<0.001). DARPP-32 immunohistochemistry revealed a significant reduction of absolute striatal lesion volume in riluzole treated animals compared to lesioned but untreated animals (P<0.01). No significant difference in counts of nigral dopaminergic neurons was found in treated versus untreated double-lesioned animals. The results of our study indicate that riluzole mediates neuroprotective effects in the double lesion rat model of MSA-P. Whether riluzole also protects autonomic and cerebellar pathways that are frequently affected in MSA remains to be determined. Nonetheless, our study is the first to provide an experimental rationale for exploring possible neuroprotective effects of riluzole in MSA.
authors.affiliation: Department of Neurology, University Hospital, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Scherfler
authors.forename: T
authors.initials: T
authors.lastname: Sather
authors.forename: E
authors.initials: E
authors.lastname: Diguet
authors.forename: N
authors.initials: N
authors.lastname: Stefanova
authors.forename: Z
authors.initials: Z
authors.lastname: Puschban
authors.forename: F
authors.initials: F
authors.lastname: Tison
authors.forename: W
authors.initials: W
authors.lastname: Poewe
authors.forename: G K
authors.initials: GK
authors.lastname: Wenning
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D003714:Denervation; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D009068:Movement / Q000187:drug effects / Q000502:physiology; D019578:Multiple System Atrophy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects; D009498:Neurotoxins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000008:administration & dosage* / Q000009:adverse effects; D013378:Substantia Nigra / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D019782:Riluzole; D016627:Oxidopamine; D017378:Quinolinic Acid