The Spinal Transcriptome after Cortical Stroke: In Search of Molecular Factors Regulating Spontaneous Recovery in the Spinal Cord

The Journal of Neuroscience, 2019 · DOI: https://doi.org/10.1523/JNEUROSCI.2571-18.2019 · Published: June 12, 2019

Neurology Neuroplasticity Neurorehabilitation

Simple Explanation

Following a stroke, the brain can sometimes recover some function spontaneously. This study looks at how the spinal cord changes at a molecular level after a stroke in the cortex. The researchers found that after a stroke, the spinal cord goes through two main phases: an early inflammatory phase and a later phase where the spinal cord promotes nerve growth. This study identifies specific molecules that could be targets for new treatments to help stroke patients recover motor function.

Study Duration

6 weeks

Participants

94 adult C57BL/6J mice (2–3 months old, mixed sex)

Evidence Level

Not specified

Key Findings

1
The spinal transcriptome after cortical stroke is characterized by two phases: an early inflammatory phase and a late tissue repair phase with upregulated genes related to neurite outgrowth.
2
Microglia are specifically activated in the denervated corticospinal projection fields in the early phase after stroke.
3
The stroke-denervated spinal gray matter, particularly its intermediate laminae, represents a growth-promoting environment for sprouting corticospinal fibers.

Research Summary

This study investigates the molecular changes in the spinal cord after cortical stroke in mice, focusing on factors that influence the reinnervation process by contralesional corticospinal neurons. The mRNA profile of the reinnervation area was analyzed using whole-genome sequencing, revealing two phases: an early inflammatory phase and a later tissue repair phase. The findings suggest that the stroke-denervated spinal gray matter represents a growth-promoting environment for sprouting corticospinal fibers, offering insights for future neuroregenerative treatments.

Practical Implications

Therapeutic Targets

Identifies potential molecular targets (e.g., Sema6a, Ntng2, TGF-β1) in the spinal cord that can be manipulated to enhance post-stroke recovery.

Timing of Intervention

Highlights the importance of timing in therapeutic interventions, suggesting that anti-inflammatory strategies may be beneficial early after stroke, while growth-promoting factors may be more effective at later stages.

Understanding Spontaneous Recovery

Provides a deeper understanding of the molecular mechanisms underlying spontaneous recovery after stroke, which can inform the development of more effective rehabilitation strategies.

Study Limitations

1
The study was conducted on mice, and the results may not be directly applicable to humans.
2
The study focused on a specific type of stroke (photothrombotic) and a specific area of the spinal cord, which may limit the generalizability of the findings.
3
The study only examined mRNA expression and did not directly assess protein levels or functional consequences of the identified changes.

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