TGFβ3 is Neuroprotective and Alleviates the Neurotoxic Response Induced by Aligned Poly-L-Lactic Acid Fibers on Naïve and Activated Primary Astrocytes

Acta Biomater., 2020 · DOI: 10.1016/j.actbio.2020.09.057 · Published: November 1, 2020

Simple Explanation

Following spinal cord injury, astrocytes become reactive and can exhibit a neurotoxic phenotype, leading to neuronal death. This study explores whether aligned poly-L-lactic acid (PLLA) microfibers, a type of biomaterial, can modulate these astrocytic phenotypes. The researchers found that PLLA fibers mildly increased the expression of neurotoxic markers in astrocytes. However, the presence of transforming growth factor β3 (TGFβ3) greatly reduced these markers and improved neuronal survival. This suggests that TGFβ3 can counteract the neurotoxic effects induced by PLLA fibers, potentially promoting a more neuroprotective environment after spinal cord injury.

Study Duration

4 days

Participants

Sprague Dawley rat pups

Evidence Level

Not specified

Key Findings

1
PLLA fibers induce a mild neurotoxic phenotype in both naïve and A1 reactive astrocytes, indicating that the fibers alone may promote a detrimental environment.
2
TGFβ3 alleviates the neurotoxic response induced by PLLA fibers, shown by the decrease in the expression of Lcn2, H2-D1 and SerpinG1.
3
TGFβ3 promotes neuronal survival in culture, suggesting its potential for neuroprotection in conjunction with PLLA fibers.

Research Summary

This study investigates the impact of aligned PLLA microfibers on astrocyte reactivity following spinal cord injury (SCI), focusing on the modulation of neurotoxic (A1) and neuroprotective (A2) astrocytic phenotypes. The findings reveal that PLLA fibers mildly increase the expression of A1-specific markers, suggesting a potential to induce a more reactive, neurotoxic phenotype in astrocytes. However, the presence of TGFβ3 significantly reduces the expression of A1-specific markers and improves neuronal survival, suggesting that TGFβ3 can alleviate the neurotoxic response induced by PLLA fibers.

Practical Implications

Biomaterial Design

The study highlights the importance of considering astrocyte phenotype modulation when designing biomaterials for SCI. PLLA fibers alone may not be sufficient and require supplementation with factors like TGFβ3.

Therapeutic Strategy

Combining PLLA fibers with TGFβ3 could be a promising therapeutic approach to target reactive astrogliosis and promote neuroprotection following SCI.

Further Research

Future studies should investigate the optimal dosage and delivery method of TGFβ3 in conjunction with PLLA fibers to maximize neuroprotective effects in vivo.

Study Limitations

1
The analysis focused on measuring gene expression changes and not the actual levels of protein produced by astrocytes.
2
Experiments were done using immature astrocytes isolated from the spinal cords of 2-day-old pups, which are not representative of the mature astrocytes found in the injury site.
3
The shift towards a neurotoxic phenotype is specific to the particular PLLA fibers used in this study and cannot be generalized to all electrospun fibers.

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