Recovery of Forearm and Fine Digit Function After Chronic Spinal Cord Injury by Simultaneous Blockade of Inhibitory Matrix Chondroitin Sulfate Proteoglycan Production and the Receptor PTPr

Journal of Neurotrauma, 2023 · DOI: 10.1089/neu.2023.0117 · Published: December 1, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries (SCI) often lead to lasting paralysis due to an inhibitory environment that hinders nerve regeneration and sprouting, especially in chronic stages. This study explores a novel treatment to improve arm and hand function in rats with chronic SCI by simultaneously blocking chondroitin sulfate proteoglycan (CSPG) production and the PTPr receptor. The combined treatment significantly improved the paralyzed forelimb and paw, as well as precision movements of the digits, suggesting a crucial role of CSPG-mediated inhibition via the PTPr receptor.

Study Duration

3 months treatment, 4 weeks follow-up

Participants

Adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
The combined treatment of ISP and PNNi significantly improved forelimb locomotor function in chronically injured rats.
2
Combination treatment led to clear improvements in paw/finger function during cereal eating, with the best-responding animals showing near-normal grasping ability.
3
Histological analyses revealed reductions in WFA+ matrix and PNNs, and sprouting of serotonin (5-HT) axons in the spinal cord of treated animals, particularly with the combined treatment.

Research Summary

This study investigates the recovery of forearm and fine digit function after chronic spinal cord injury (SCI) in rats, using a novel treatment strategy that simultaneously blocks chondroitin sulfate proteoglycan (CSPG) production and the PTPr receptor. The combined treatment, consisting of an intracellular sigma peptide (ISP) and a perineuronal net inhibitor (PNNi), showed a profound effect on functional recovery of the chronically paralyzed forelimb and paw, as well as on precision movements of the digits. Histological analyses revealed that the treatment led to reductions in CSPGs, increased serotonergic fiber density, and the clearance of CSPG aggregates in the dorsomedial corticospinal tract, suggesting a potential mechanism for the observed functional improvements.

Practical Implications

Clinical Translation

The study suggests a potential clinically relevant translational benefit by targeting CSPG-mediated inhibition via the PTPr receptor to enhance functional synaptic plasticity.

Therapeutic Strategy

Systemic administration of ISP and PNNi presents a non-invasive therapeutic approach for improving motor function after chronic SCI.

Combination Therapy

The combination of ISP and PNNi demonstrates synergistic effects in promoting fine motor recovery compared to individual treatments.

Study Limitations

1
The precise mechanisms of action of PNNi plus ISP remains unknown.
2
The origin and biological impact of the WFA+ plaques must await further studies.
3
The anatomical substrate (whether it be newly sprouted or latent) that underlies such robust functional recovery chronically is unknown.

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