Intraspinal MDL28170 microinjection improves functional and pathological outcome following spinal cord injury

Chen Guang Yu, Aashish Joshi, James W. Geddes

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Although calpain (calcium-activated cysteine protease) inhibition represents a rational therapeutic target for spinal cord injury (SCI), few studies have reported improved functional outcomes with post-injury administration of calpain inhibitors. This reflects the weak potency and limited aqueous solubility of current calpain inhibitors. Previously, we demonstrated that intraspinal microinjection of the calpain inhibitor MDL28170 resulted in greater inhibition of calpain activity as compared to systemic administration of the same compound. In the present study, we evaluated the ability of intraspinal MDL28170 microinjection to spare spinal tissue and locomotor dysfunction following SCI. Contusion SCI was produced in female Long-Evans rats using the Infinite Horizon impactor at the 200-kdyn force setting. Open-field locomotion was evaluated until 6 weeks post-injury. Histological assessment of tissue sparing was performed at 6 weeks after SCI. The results demonstrate that MDL28170, administered with a single post-injury intraspinal microinjection (50 nmoles), significantly improves both locomotor function and pathological outcome measures following SCI.

Original languageEnglish
Pages (from-to)833-840
Number of pages8
JournalJournal of Neurotrauma
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2008

Funding

FundersFunder number
National Institute of Neurological Disorders and StrokeR01NS045726

    Keywords

    • Locomotion
    • Neurodegeneration
    • Neuroprotection
    • White matter sparing

    ASJC Scopus subject areas

    • Clinical Neurology

    Fingerprint

    Dive into the research topics of 'Intraspinal MDL28170 microinjection improves functional and pathological outcome following spinal cord injury'. Together they form a unique fingerprint.

    Cite this