Weakened rate-dependent depression of Hoffmann's reflex and increased motoneuron hyperactivity after motor cortical infarction in mice.

Abstract

Abnormal reflexes associated with spasticity are considered a major determinant of motor impairments occurring after stroke; however, the mechanisms underlying post-stroke spasticity remain unclear. This may be because of the lack of suitable rodent models for studying spasticity after cortical injuries. Thus, the purpose of the present study was to establish an appropriate post-stroke spasticity mouse model. We induced photothrombotic injury in the rostral and caudal forelimb motor areas of mice and used the rate-dependent depression (RDD) of Hoffmann's reflex (H-reflex) as an indicator of spastic symptoms. To detect motoneuron excitability, we examined c-fos mRNA levels and c-Fos immunoreactivity in affected motoneurons using quantitative real-time reverse transcription PCR and immunohistochemical analysis, respectively. To confirm the validity of our model, we confirmed the effect of the anti-spasticity drug baclofen on H-reflex RDDs 1 week post stroke. We found that 3 days after stroke, the RDD was significantly weakened in the affected muscles of stroke mice compared with sham-operated mice, and this was observed for 8 weeks. The c-fos mRNA levels in affected motoneurons were significantly increased in stroke mice compared with sham-operated mice. Immunohistochemical analysis revealed a significant increase in the number of c-Fos-positive motoneurons in stroke mice compared with sham-operated mice at 1, 2, 4, and 8 weeks after stroke; however, the number of c-Fos-positive motoneurons on both sides of the brain gradually decreased over time. Baclofen treatment resulted in recovery of the weakened RDD at 1 week post stroke. Our findings suggest that this is a viable animal model of post-stroke spasticity.

• Authors: S Lee, T Toda, H Kiyama, T Yamashita
• Journal: Cell death & disease (Cell Death Dis) Vol. 5 Pg. e1007 (Jan 16 2014) ISSN: 2041-4889 [Electronic] England
• PMID: 24434515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-fos
• Baclofen

Topics

• Animals
• Baclofen (administration & dosage)
• Cerebral Infarction (complications)
• Disease Models, Animal
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Motor Neurons (chemistry, drug effects, physiology)
• Muscle Weakness (drug therapy, etiology, physiopathology)
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Reflex, Abnormal