Deep Brain Stimulation in the Subthalamic Nucleus Can Improve Skilled Forelimb Movements and Retune Dynamics of Striatal Networks in a Rat Stroke Model

Int J Mol Sci. 2022 Dec 14;23(24):15862. doi: 10.3390/ijms232415862.

Abstract

Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single-pellet reaching (SPR) test after stroke and determined costimulated brain regions during STN-HFS using 2-[18F]Fluoro-2-deoxyglucose-([18F]FDG)-positron emission tomography (PET). After a 4-week training of SPR, photothrombotic stroke was induced in the sensorimotor cortex of the dominant hemisphere. Thereafter, an electrode was implanted in the STN ipsilateral to the infarction, followed by a continuous STN-HFS or sham stimulation for 7 days. On postinterventional day 2 and 7, an SPR test was performed during STN-HFS. Success rate of grasping was compared between these two time points. [18F]FDG-PET was conducted on day 2 and 3 after stroke, without and with STN-HFS, respectively. STN-HFS resulted in a significant improvement of SPR compared to sham stimulation. During STN-HFS, a significantly higher [18F]FDG-uptake was observed in the corticosubthalamic/pallidosubthalamic circuit, particularly ipsilateral to the stimulated side. Additionally, STN-HFS led to an increased glucose metabolism within the brainstem. These data demonstrate that STN-HFS supports rehabilitation of skilled forelimb movements, probably by retuning dysfunctional motor centers within the cerebral network.

Keywords: [18F]FDG positron emission tomography; experimental stroke; invasive electric stimulation; neuronal network; photothrombosis; skilled forelimb movements; subthalamic nucleus.

MeSH terms

  • Animals
  • Deep Brain Stimulation* / methods
  • Fluorodeoxyglucose F18 / metabolism
  • Forelimb
  • Rats
  • Stroke* / diagnostic imaging
  • Stroke* / metabolism
  • Stroke* / therapy
  • Subthalamic Nucleus* / diagnostic imaging
  • Upper Extremity

Substances

  • Fluorodeoxyglucose F18