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  4. GDNF reverses the inhibitory properties of reactive astrocytes allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury

GDNF reverses the inhibitory properties of reactive astrocytes allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury

Exp Neurol, 2011 · DOI: 10.1016/j.expneurol.2011.02.001 · Published: June 1, 2011

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This study investigates how a protein called GDNF, combined with Schwann cells (SCs), can help nerves regenerate after spinal cord injury. Reactive astrocytes, a type of brain cell, usually prevent nerve regeneration after injury. The researchers found that GDNF can reverse the inhibitory properties of these astrocytes, allowing nerves to regenerate through channels containing SCs. The astrocytes, under the influence of GDNF, even migrated into these channels and supported nerve growth. In lab experiments, GDNF caused SCs and astrocytes to move towards each other and reduced the production of substances that inhibit nerve growth. This suggests that GDNF can modify the behavior of astrocytes, turning them from inhibitors to promoters of nerve regeneration.

Study Duration
6 weeks
Participants
Adult female SD rats (180-200 grams)
Evidence Level
Not specified

Key Findings

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    GDNF, combined with transplanted Schwann cells (SCs), effectively reversed the inhibitory properties of astrocytes at graft-host interfaces allowing robust axonal regeneration.
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    GDNF induced migration of SCs and astrocytes toward each other in an astrocyte-SC confrontation assay and enhanced migration of astrocytes on a SC monolayer.
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    GDNF treatment significantly reduced production of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs), two hallmarks of astrogliosis, in both the in vivo and in vitro models.

Research Summary

This study demonstrates that GDNF can modify the astrogliotic response following spinal cord injury, promoting axonal regeneration into Schwann cell grafts. GDNF facilitates the migration of astrocytes into SC grafts, reduces GFAP and CSPG expression, and promotes alignment of astrocytes with regenerating axons. The modification of reactive astrocyte properties by GDNF represents a novel strategy to promote axonal regeneration and functional recovery after spinal cord injury.

Practical Implications

Therapeutic Target

GDNF could be used as a therapeutic agent to promote axonal regeneration after spinal cord injury.

Combination Therapy

Combining GDNF with Schwann cell transplantation may enhance nerve regeneration and functional recovery.

Modifying Astrogliosis

Targeting the inhibitory properties of reactive astrocytes offers a new avenue for spinal cord injury treatment.

Study Limitations

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