The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Neural Plasticity, 2018 · DOI: https://doi.org/10.1155/2018/2952386 · Published: April 18, 2018

Simple Explanation

The extracellular environment in the central nervous system (CNS) plays a critical role in its function and stability. This review focuses on how components like the extracellular matrix (ECM) and myelin regulate CNS plasticity. After an injury to the CNS, the ECM and myelin create an environment that inhibits axonal regeneration. Unlike the peripheral nervous system, the CNS cannot revert to a developmental state to aid in repair. Modulating external factors like the ECM and myelin has been shown to promote growth, regeneration, and functional plasticity after injury. This review highlights factors that either contribute to or prevent these processes after spinal cord injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
CSPGs and tenascins, which form perineuronal nets (PNNs), enhance synaptic stability in the adult CNS but contribute to the inhibitory glial scar after injury, preventing axonal regeneration.
2
Myelin sheaths and mature oligodendrocytes, while essential for signal conduction, contribute to the inhibitory environment after injury, limiting the CNS's ability to repair itself.
3
Myelin-associated inhibitors (MAIs) like Nogo, OMgp, and MAG inhibit neurite outgrowth and influence plasticity in the CNS, preventing structural plasticity that could be detrimental to physiological function.

Research Summary

The review discusses how the extracellular environment of the CNS, particularly the ECM and myelin, influences plasticity, sprouting, and axonal regeneration after spinal cord injury. It highlights the inhibitory roles of CSPGs, tenascins, and myelin-associated inhibitors (MAIs) in preventing axonal regeneration after CNS injury, contrasting with the regenerative capacity of the peripheral nervous system. Therapeutic strategies targeting the removal or degradation of myelin debris and CSPGs have shown promise for CNS repair, suggesting that modulation of the extracellular environment can promote axonal growth and functional recovery.

Practical Implications

Targeting MAIs for CNS Repair

Neutralizing myelin-associated inhibitors (MAIs) like Nogo-A, OMgp, and MAG can promote neurite outgrowth and axonal regeneration after SCI. Clinical trials are underway to assess anti-Nogo-A antibodies for stroke and SCI treatment.

Modulating CSPGs to Enhance Plasticity

Enzymatic inactivation of CSPGs using chondroitinase ABC (ChABC) can promote axonal plasticity and regeneration in models of SCI, leading to improved sensory and proprioceptive behavioral recovery.

Combinatorial Therapeutic Approaches

Combining strategies that address both the extracellular and intracellular environments of neurons may offer the best opportunity for achieving successful repair after SCI, rather than relying on a single-target approach.

Study Limitations

1
The review primarily focuses on CSPGs and myelin, with less discussion on other ECM components.
2
The review acknowledges conflicting reports regarding the precise roles of some molecules, such as OMgp, requiring further investigation.
3
The review is limited by the inherent complexity of SCI and the CNS environment, making it challenging to fully capture all contributing factors.

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