Thalamic deep brain stimulation improves movement in a cerebellar model of lesion-based status dystonicus.

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Tác giả: Amanda M Brown, Jason S Gill, Tao Lin, Megan X Nguyen, Roy V Sillitoe

Ngôn ngữ: eng

Ký hiệu phân loại: 594.38 *Pulmonata

Thông tin xuất bản: United States : Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 56406

 Dystonia is the third most common movement disorder and an incapacitating co-morbidity in a variety of neurologic conditions. Dystonia can be caused by genetic, degenerative, idiopathic, and acquired etiologies, which are hypothesized to converge on a "dystonia network" consisting of the basal ganglia, thalamus, cerebellum, and cerebral cortex. In acquired dystonia, focal lesions to subcortical network regions lead to dystonia that can be difficult to manage with canonical treatments, including deep brain stimulation (DBS). While studies in animal models have begun to parse the contribution of individual nodes in the dystonia network, how acquired injury to the cerebellar outflow tracts instigates dystonia
  and how network modulation interacts with symptom latency remain unexplored questions. Here, we present an electrolytic lesioning paradigm that bilaterally targets the cerebellar outflow tracts. We found that lesioning these tracts, at the junction of the superior cerebellar peduncles and the medial and intermediate cerebellar nuclei, resulted in transient, acute, and severe dystonia with immobility and fixed posturing similar to status dystonicus. We observed a rapid reduction in dystonia with 1 ​h of DBS of the centrolateral thalamic nucleus, a first order node in the network downstream of the cerebellar nuclei. In contrast, 1 ​h of stimulation at a second order node in the short latency, disynaptic projection from the cerebellar nuclei, the striatum, did not show similar rapid modulation of dystonia. Our study introduces a robust paradigm for inducing acute, severe dystonia, and demonstrates that targeted modulation based on network principles powerfully rescues motor behavior. These data inspire the identification of a short latency therapeutic target for acquired dystonia and status dystonicus.
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