The effects of human immunoglobulin G on enhancing tissue protection and neurobehavioral recovery after traumatic cervical spinal cord injury are mediated through the neurovascular unit

Journal of Neuroinflammation, 2019 · DOI: https://doi.org/10.1186/s12974-019-1518-0 · Published: June 11, 2019

Simple Explanation

Spinal cord injury (SCI) is a devastating condition with limited effective treatments. The body's immune response after SCI can worsen the damage. This study explores using human immunoglobulin G (hIgG), a substance known to modulate the immune system, to improve recovery after SCI in rats. Rats with SCI were treated with different doses of hIgG, a control substance, or methylprednisolone (MPSS), a standard treatment. Researchers then analyzed the effects of these treatments on spinal cord tissue, inflammation, and the rats' ability to move and function. The study found that a high dose of hIgG (2 g/kg) showed promise in protecting the spinal cord's blood vessels, reducing inflammation, and improving recovery of movement and function in rats with SCI. These effects were comparable to the standard treatment, MPSS.

Study Duration

6 weeks

Participants

124 female adult Wistar rats

Evidence Level

Not specified

Key Findings

1
hIgG (2 g/kg) protected the spinal cord neurovasculature after SCI by increasing tight junction protein expression and reducing inflammatory enzyme expression.
2
hIgG (2 g/kg) increased serum expression of inflammatory cytokines and co-localized (without decreasing protein expression) with spinal cord vascular cell adhesion molecule-1.
3
Acute molecular benefits of hIgG (2 g/kg) led to greater tissue preservation, functional blood flow, and neurobehavioral recovery at 6 weeks post-SCI.

Research Summary

This study investigated the dose-dependent effects of intravenously administered hIgG on neuroinflammation after SCI in rats, demonstrating that hIgG (2 g/kg) is more effective than hIgG (0.4 g/kg) in treating SCI. High-dose hIgG (2 g/kg) exerts protective effects on the spinal cord vasculature by reducing neutrophil infiltration, decreasing pro-inflammatory enzyme expression, and fostering an anti-inflammatory environment in the spinal cord. These protective effects contribute to decreased lesion volume and enhanced functional blood flow after SCI, ultimately improving tissue preservation and neurobehavioral recovery.

Practical Implications

Therapeutic Potential

hIgG (2 g/kg) shows promise as a therapeutic approach for mitigating secondary pathology in SCI by antagonizing immune cell infiltration at the neurovascular unit level.

Clinical Translation

Further optimization of hIgG efficacy and delineation of its mechanisms are required before clinical use for SCI, including studying clinically relevant administration time points and identifying the active component of the hIgG molecule.

Immunomodulatory Strategies

The study supports the growing trend of using immunomodulatory, rather than immunosuppressive, strategies to treat SCI, highlighting the potential benefits of modulating the immune response without causing systemic immune deficiency.

Study Limitations

1
Polymorphisms and interspecies differences of hIgG influence the binding of IgG to Fcγ receptors (FcγRs) and may alter the downstream signaling cascades.
2
Further optimization of efficacy and delineating its mechanism are required before hIgG can be used in the clinic to treat SCI.
3
Determining which component of the hIgG molecule mediates the observed immunomodulatory effects.

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