Transsynaptic degeneration of ventral horn motor neurons exists but plays a minor role in lower motor system dysfunction in acute ischemic rats

PLoS One. 2024 Apr 26;19(4):e0298006. doi: 10.1371/journal.pone.0298006. eCollection 2024.

Abstract

Background: As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated.

Methods: Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed.

Results: At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process.

Conclusions: This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Anterior Horn Cells* / pathology
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Disease Models, Animal
  • Male
  • Microglia / pathology
  • Motor Neurons / pathology
  • Motor Neurons / physiology
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / pathology
  • Synapses / physiology

Grants and funding

This work was supported by Beijing Natural Science Foundation (7202158), National High Level Hospital Clinical Research Funding (2022-PUMCH-B-017), and CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-003). All funding was awarded to MSL. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.