Blood–spinal cord barrier pericyte reductions contribute to increased capillary permeability

Journal of Cerebral Blood Flow & Metabolism, 2012 · DOI: 10.1038/jcbfm.2012.113 · Published: August 1, 2012

Spinal Cord Injury Cardiovascular Science Neurology

Simple Explanation

The blood-spinal cord barrier (BSCB) regulates the passage of molecules between the blood and the spinal cord, which is crucial for proper nerve function. Pericytes, cells surrounding blood vessels, are thought to be key components of this barrier. This study found that pericytes are less abundant in spinal cord capillaries compared to those in the brain, particularly in the anterior horn of the spinal cord. This regional difference is linked to increased permeability of the spinal cord capillaries and reduced expression of certain proteins that form tight junctions in the endothelial cells. When pericytes were reduced in mice, the BSCB became more permeable, leading to leakage of blood proteins and motor neuron loss. These results suggest pericytes are important for maintaining the integrity of the BSCB, and their reduction can lead to barrier dysfunction and nerve damage.

Study Duration

Not specified

Participants

Wild-type mice, PdgfrbF7/F7 mice, and nontransgenic littermates

Evidence Level

Not specified

Key Findings

1
Spinal cord capillaries, especially in the anterior horn, have fewer pericytes compared to brain capillaries in wild-type mice.
2
The reduced pericyte coverage in the spinal cord correlates with increased permeability of the BSCB to molecules of various sizes (350Da, 40,000Da, and 150,000Da).
3
Pericyte deficiency leads to increased accumulation of serum proteins, thrombin, and fibrin in motor neurons, resulting in motor neuron loss.

Research Summary

This study investigates the role of pericytes in the blood–spinal cord barrier (BSCB). It demonstrates that pericyte coverage and number are reduced in spinal cord capillaries compared to the brain, particularly in the anterior horn. The study reveals a strong correlation between reduced pericyte coverage and increased BSCB permeability to various molecular weight tracers. This heightened permeability is associated with diminished expression of tight junction proteins (ZO-1 and occludin). Using pericyte-deficient mice, the study further shows that reduced pericytes exacerbate BSCB disruption, leading to the accumulation of neurotoxic proteins in motor neurons and subsequent motor neuron loss, suggesting pericytes are crucial for BSCB integrity and neuronal survival.

Practical Implications

Understanding Spinal Cord Diseases

The findings provide insights into the cellular mechanisms underlying BSCB dysfunction in spinal cord diseases, such as amyotrophic lateral sclerosis and multiple sclerosis.

Targeted Therapies

The research suggests that targeting pericytes could be a potential therapeutic strategy to restore BSCB integrity and prevent neuronal damage in spinal cord disorders.

Biomarker Development

The study highlights the importance of pericyte coverage and tight junction protein expression as potential biomarkers for assessing BSCB integrity in clinical settings.

Study Limitations

1
The study primarily uses mouse models, and further research is needed to validate these findings in humans.
2
The exact mechanisms of motor neuron cell death caused by pericyte deficiency are not fully elucidated.
3
The study does not fully explore the potential contribution of other cell types (e.g., astrocytes) to BSCB integrity.

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