Pericytes impair capillary blood flow and motor function after chronic spinal cord injury

Nat Med, 2017 · DOI: 10.1038/nm.4331 · Published: June 1, 2017

Spinal Cord Injury Cardiovascular Science Neurology

Simple Explanation

After a spinal cord injury (SCI), the spinal cord below the injury site experiences reduced blood flow and oxygen, a condition called hypoxia. This is due to the increased activity of certain receptors on cells called pericytes, which constrict capillaries, the smallest blood vessels. Pericytes, after SCI, produce trace amines from dietary amino acids due to increased levels of an enzyme called AADC. These trace amines then activate receptors that cause the pericytes to constrict capillaries. Treatments that block these receptors or inhibit the AADC enzyme can improve blood flow and oxygen levels, leading to improved motor function after SCI. This suggests that alleviating chronic hypoxia could be a beneficial approach for rehabilitation after SCI.

Study Duration

2-4 months post injury

Participants

Adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
SCI leads to chronic hypoxia in the spinal cord below the injury site due to excessive capillary tone.
2
Pericytes in capillaries express AADC after SCI, synthesizing trace amines from dietary amino acids.
3
Trace amines activate 5-HT1B and α2-adrenergic receptors on pericytes, constricting capillaries.

Research Summary

This study demonstrates that pericytes play a major role in regulating capillary tone and blood flow in the spinal cord after SCI, leading to chronic hypoxia. The researchers found that AADC expressed in capillary pericytes synthesizes trace amines from dietary amino acids, which activate monoamine receptors and cause capillary constriction. Antagonism of monoamine receptors, inhibition of AADC enzyme function, or augmentation of inhaled O2 or CO2 after SCI produces lasting improvements in blood flow and cord oxygenation, ultimately improving motor function.

Practical Implications

Therapeutic Target

Pericytes are identified as a key therapeutic target for improving blood flow and oxygenation after SCI.

Pharmacological Interventions

Monoamine receptor antagonists and AADC inhibitors show potential for alleviating hypoxia and improving motor function.

Rehabilitation Strategies

Augmenting inhaled oxygen or carbon dioxide may improve blood flow, oxygenation, and motor function after SCI.

Study Limitations

1
The study was conducted on rats, and findings may not directly translate to humans.
2
The long-term effects of alleviating chronic hypoxia after SCI were not fully explored.
3
The specific mechanisms by which increased oxygenation modulates neuronal function require further investigation.

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