The Thrombin Receptor Modulates Astroglia-Neuron Trophic Coupling and Neural Repair after Spinal Cord Injury

Glia, 2021 · DOI: 10.1002/glia.24012 · Published: September 1, 2021

Simple Explanation

This study investigates how blocking the thrombin receptor, PAR1, impacts recovery after spinal cord injury (SCI) in mice. The researchers found that mice lacking PAR1 had better sensorimotor coordination, improved neuron survival, and enhanced myelin repair after SCI. Additionally, experiments with cultured cells suggested that astrocytes (a type of brain cell) lacking PAR1 promote neuron survival and neurite outgrowth, potentially through a mechanism involving a growth factor receptor called TrkB.

Study Duration

30 d

Participants

Adult female PAR1+/+ (C57BL6/J mice) or PAR1−/− mice

Evidence Level

Not specified

Key Findings

1
Genetic blockade of PAR1 in female mice results in improvements in sensorimotor co-ordination after thoracic spinal cord lateral compression injury.
2
The number of neurons positive for NeuN in the spinal cord ventral horn was 3.8-fold higher in the injury Epicenter of PAR1−/− compared to PAR1+/+ at 30 d after injury
3
PAR1 knockout astrocytes also promoted neuron survival at 24 and 72 h time points in culture.

Research Summary

This study demonstrates that genetic knockout of PAR1 in mice improves sensorimotor outcomes and neural repair after spinal cord injury. The improved outcomes are associated with reduced inflammation, increased neuron survival, enhanced myelin repair, and a shift in astrocyte phenotype towards a pro-repair state. In vitro experiments suggest that astrocytes lacking PAR1 promote neuron survival and neurite outgrowth, potentially through a TrkB-dependent mechanism involving BDNF signaling.

Practical Implications

Therapeutic Target

PAR1 could be a therapeutic target for promoting neural repair after SCI.

Astrocyte Modulation

Modulating astrocyte activity via PAR1 inhibition may enhance recovery from SCI.

Neurotrophic Coupling

PAR1 plays a role in neurotrophic coupling between astrocytes and neurons, influencing neural resilience and repair.

Study Limitations

1
The study was conducted only on female mice.
2
The precise mechanisms by which PAR1 influences glial and neuronal responses require further investigation.
3
The study used a genetic knockout model; the effects of pharmacological PAR1 inhibition may differ.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury