Spinal Cord Injury & Regeneration: Pre-clinical repair

Why is there no spontaneous axon regeneration after SCI?

Because adult CNS neurons lack intrinsic growth programs and the injury environment contains active inhibitory molecules such as CSPGs, myelin debris, and fibrotic cores.

What defines the lesion epicentre?

The lesion epicentre is the region of maximal tissue destruction containing axonal loss, inflammation, cystic cavities, and high concentrations of inhibitory molecules.

Name two intrinsic barriers to axon regeneration

Silencing of developmental growth genes and activation of growth-inhibitory pathways such as PTEN and Notch signalling

What cells initiate the acute inflammatory response after SCI?

Resident microglia and astrocytes, followed by infiltrating macrophages and neutrophils

What is the role of reactive astrocytes?

They contain the lesion by forming an astrocytic barrier but also inhibit axon regeneration by producing CSPGs.

Why are CSPGs inhibitory?

They stiffen the extracellular matrix and bind neuronal receptors (e.g. PTPσ), activating growth-inhibitory signalling.

How does chondroitinase ABC promote regeneration?

By enzymatically degrading CSPGs, making the extracellular matrix more permissive to axon growth.

What is the difference between neuroprotection and regeneration?

Neuroprotection preserves existing neurons and axons, whereas regeneration involves growth of new axons.

Why is minocycline effective in SCI models?

It reduces inflammation, microglial activation, lesion size, and secondary neuronal loss.

How does treadmill exercise improve recovery?

By enhancing functional plasticity, strengthening spared pathways, and improving conduction without inducing new axon growth.

What is functional plasticity?

Reorganisation and strengthening of existing neural circuits to compensate for lost connections.

What is the role of electrical stimulation after SCI?

It promotes activity-dependent rewiring and induces new functional neuron states that support motor recovery.

Why are pericytes relevant to scarring?

They contribute to fibrotic scar/core formation, which creates a stiff physical barrier to axon regeneration.

Why do neonatal mice regenerate better after SCI?

Their microglia promote scar-free healing and produce proteases that prevent inhibitory scar formation.

How does Taxol promote axon regeneration?

By stabilising microtubules, preventing retraction bulb formation, and supporting axon elongation.

What advantage do spinal cord-derived NSCs have?

They are region-matched and support robust axonal regeneration and synapse formation.

Why is PTEN deletion so effective?

PTEN is a major intrinsic growth brake; its deletion reactivates mTOR-dependent axon growth pathways.

What is the role of epigenetic regulation in regeneration?

Opening chromatin via histone acetylation re-enables expression of growth-associated genes.

What does Lin28a do in regeneration?

It reactivates developmental growth programs, promoting long-distance CST regeneration.

Why are combinatorial therapies necessary?

Because regeneration requires overcoming both intrinsic neuronal limitations and extrinsic environmental inhibition.