Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat

Y Cao; J S Shumsky; M A Sabol; R A Kushner; S Strittmatter; F P T Hamers; D H S Lee; S A Rabacchi; M Murray

doi:10.1177/1545968307308550

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Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat

Journal article

Open access

Peer reviewed

Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat

Y Cao, J S Shumsky, M A Sabol, R A Kushner, S Strittmatter, F P T Hamers, D H S Lee, S A Rabacchi and M Murray

Neurorehabilitation and neural repair, v 22(3), pp 262-278

May 2008

DOI: https://doi.org/10.1177/1545968307308550

PMID: 18056009

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Animals

Behavior, Animal - drug effects

Denervation

Efferent Pathways - drug effects

Efferent Pathways - metabolism

Efferent Pathways - physiopathology

Female

GPI-Linked Proteins

Growth Cones - drug effects

Growth Cones - metabolism

Myelin Proteins - antagonists & inhibitors

Myelin Proteins - metabolism

Myelin Proteins - pharmacology

Myelin Proteins - therapeutic use

Nerve Regeneration - drug effects

Nerve Regeneration - physiology

Neuronal Plasticity - drug effects

Neuronal Plasticity - physiology

Nogo Receptor 1

Peptide Fragments - pharmacology

Peptide Fragments - therapeutic use

Pyramidal Tracts - drug effects

Pyramidal Tracts - metabolism

Pyramidal Tracts - physiopathology

Raphe Nuclei - drug effects

Raphe Nuclei - metabolism

Rats

Rats, Sprague-Dawley

Receptors, Cell Surface - antagonists & inhibitors

Receptors, Cell Surface - metabolism

Recovery of Function - drug effects

Recovery of Function - physiology

Red Nucleus - drug effects

Red Nucleus - metabolism

Spinal Cord Injuries - drug therapy

Spinal Cord Injuries - metabolism

Spinal Cord Injuries - physiopathology

Spinal Nerve Roots - drug effects

Spinal Nerve Roots - metabolism

Treatment Outcome

Wallerian Degeneration - drug therapy

Wallerian Degeneration - metabolism

Wallerian Degeneration - physiopathology

The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons.

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87 citations in Web of Science

88 citations in Scopus

Details

Title: Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
Creators: Y Cao - Drexel University
J S Shumsky - Drexel University
M A Sabol - Drexel University
R A Kushner - Drexel University
S Strittmatter - Yale University
F P T Hamers - Utrecht University
D H S Lee - Lundbeck
S A Rabacchi - Lundbeck
M Murray - Drexel University
Publication Details: Neurorehabilitation and neural repair, v 22(3), pp 262-278
Publisher: Sage
Grant note: R01 NS056485 / NINDS NIH HHS P50 NS024707 / NINDS NIH HHS R37 NS033020-17 / NINDS NIH HHS R37 NS033020 / NINDS NIH HHS R01 NS039962-10 / NINDS NIH HHS R01 NS042304 / NINDS NIH HHS R01 NS042304-08 / NINDS NIH HHS T32HD07467 / NICHD NIH HHS NS24707 / NINDS NIH HHS R01 NS039962 / NINDS NIH HHS T32 HD007467 / NICHD NIH HHS R01 NS056485-04 / NINDS NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Neurobiology and Anatomy
Web of Science ID: WOS:000255962000005
Scopus ID: 2-s2.0-42449104410
Other Identifier: 991019168440204721

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Web of Science research areas: Clinical Neurology; Rehabilitation

Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat

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Abstract

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UN Sustainable Development Goals (SDGs)

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