Intrinsic response of thoracic propriospinal neurons to axotomy

BMC Neuroscience, 2010 · DOI: 10.1186/1471-2202-11-69 · Published: June 4, 2010

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following spinal cord injury (SCI), axons in the central nervous system (CNS) don't regenerate well. However, propriospinal (PS) neurons, which are located within the spinal cord, show a better regenerative response than other neurons. This study investigates the response of these PS neurons after spinal cord injury. Researchers used techniques to analyze gene expression in thoracic PS neurons after SCI. They found that genes related to the immune response were strongly activated early after injury, along with genes associated with regeneration and cell survival. However, some pro-apoptotic genes also increased, suggesting cell death in some neurons. The results suggest that thoracic PS neurons have a dynamic response to injury, including both a regenerative attempt and cell death. The immune response may play a key role in both processes. Also, administering growth factors early after injury might protect these neurons and support regeneration.

Study Duration

3-days to 1-month

Participants

36 female hooded Long-Evans rats

Evidence Level

Not specified

Key Findings

1
A strong and early upregulation occurs in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week post-injury.
2
Several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest post-injury period studied.
3
Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred only during the initial period examined.

Research Summary

The study examines the intrinsic post-axotomy response of thoracic propriospinal (TPS) neurons following spinal cord injury (SCI), focusing on changes in gene expression at different time points. The research reveals a dynamic response that includes a strong regenerative response, a significant upregulation of genes involved in the immune/inflammatory response, and the cell death of many axotomized TPS neurons in the first week after SCI. The findings suggest that the immune/inflammatory response may play an important role in mediating the early strong regenerative response, as well as the apoptotic response. The up-regulation in the expression of genes for several growth factor receptors during the first week post-SCI also suggest that administration of these factors may protect TPS neurons from cell death and maintain a regenerative response, but only if given during the early period after injury.

Practical Implications

Therapeutic interventions

Early administration of growth factors such as GDNF, LIF and CNTF may protect axotomized PS neurons from apoptosis.

Regenerative strategies

The findings highlight the potential of targeting the early inflammatory response to promote a more sustained regenerative response in TPS neurons.

Clinical relevance

Understanding the molecular mechanisms underlying TPS neuron response to SCI may lead to novel therapeutic targets for promoting functional recovery.

Study Limitations

1
The complex experimental design and small sample sizes per group may have resulted in an overly stringent FDR correction.
2
Microglial/macrophage contamination during laser microdissection cannot be completely excluded.
3
The study focused on a specific type of neuron (TPS) and may not be generalizable to all propriospinal neurons or other CNS neurons.

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