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.
MeSH terms
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Animals
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Biomarkers / metabolism
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Corpus Striatum / drug effects*
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Corpus Striatum / injuries
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Corpus Striatum / physiopathology
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Denervation
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Disease Models, Animal
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Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
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Excitatory Amino Acid Antagonists / administration & dosage
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Excitatory Amino Acid Antagonists / adverse effects
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Male
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Medial Forebrain Bundle / injuries
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Medial Forebrain Bundle / physiopathology
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Medial Forebrain Bundle / surgery
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Movement / drug effects
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Movement / physiology
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Multiple System Atrophy / drug therapy*
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Multiple System Atrophy / metabolism
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Multiple System Atrophy / physiopathology
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / physiopathology
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Nerve Degeneration / prevention & control
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Neurons / drug effects*
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Neurons / metabolism
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Neurons / pathology
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / adverse effects
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Neurotoxins
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Oxidopamine
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Quinolinic Acid
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Rats
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Rats, Wistar
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Riluzole / administration & dosage*
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Riluzole / adverse effects
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Substantia Nigra / injuries
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Substantia Nigra / physiopathology
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Substantia Nigra / surgery
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Treatment Outcome
Substances
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Biomarkers
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Neurotoxins
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Riluzole
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Oxidopamine
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Quinolinic Acid