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  4. Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

JOURNAL OF NEUROTRAUMA, 2014 · DOI: 10.1089/neu.2013.3143 · Published: May 1, 2014

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Following a spinal cord injury (SCI), axons often fail to regenerate due to the build-up of chondroitin sulfate proteoglycans (CSPG). This study examines how treatment with chondroitinase ABC (ChABC), an enzyme that breaks down CSPGs, affects astrocyte behavior and blood vessel regrowth, both of which are crucial for axon regeneration. The research found that ChABC treatment effectively cleared CSPGs, stimulated axon remodeling, and caused astrocytes to reorient towards the injury site, working in tandem with axons. Additionally, it initially disrupted blood vessel structure but later promoted the formation of healthy new vessels. The findings suggest that ChABC, when combined with other treatments, holds promise as a therapeutic approach for SCI repair by reducing the physical and chemical barriers to axon regrowth.

Study Duration
10 weeks
Participants
50 adult female Wistar rats
Evidence Level
Not specified

Key Findings

  • 1
    ChABC treatment effectively cleaves CSPG glycosaminoglycan chains and stimulates axonal remodeling within the injury site, accompanied by an extended period of astrocyte remodeling.
  • 2
    ChABC treatment favored an orientation of astrocytic processes directed toward the injury, in close association with axons at the lesion entry zone, suggesting a correlation between axon and astrocyte remodeling.
  • 3
    During the first weeks post-injury, ChABC treatment affected the morphology of laminin-positive blood vessel basement membranes and vessel-independent laminin deposits, but at later time points, laminin expression increased and became more directly associated with newly formed blood vessels.

Research Summary

This study investigates the effects of ChABC treatment on astrogliosis and revascularization after spinal cord injury (SCI) in rats. The researchers injected ChABC intrathecally after a spinal cord hemisection and analyzed the impact on CSPG cleavage, astrocyte remodeling, and blood vessel morphology. The findings indicate that ChABC treatment not only reduces the chemical barrier to axon remodeling by cleaving CSPGs but also modifies the physical barrier by influencing astrocyte dynamics and revascularization. The study concludes that ChABC treatment, in combination with other therapies, shows promise for SCI repair by promoting a more efficient revascularization of the lesion site and close association between growing axons and astrocytic processes.

Practical Implications

Therapeutic Strategy for SCI Repair

ChABC injection in combination with other synergistic treatments is a promising therapeutic strategy for SCI repair.

Modulation of Glial Scar

ChABC treatment reduces not only the chemical, but also the physical barrier to axon remodeling, while at the same time increasing astrocyte dynamics and remodeling.

Efficient Revascularization

ChABC treatment ultimately favors formation of neovessels exhibiting a BM closely resembling that of vessels in intact tissue.

Study Limitations

  • 1
    ChABC treatment alone is not sufficient for complete repair.
  • 2
    The experimental model does not allow to exclude that, on the contrary, growing axons might play a role in guiding astrocyte processes.
  • 3
    Extravasation of IgG at all time points post-injury and found that ChABC treatment does not affect BSCB restoration after SCI

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