MULTICENTER SPINAL CORD INJURY STUDY

Project Details

Description

The second National Acute Spinal Cord Injury Study (NASCIS 2) showed that
methylprednisolone (MP) improved neurologic recovery in human spinal cord
injury (SCI) but the treatment has a strictly limited therapeutic window.
To identify better treatments, laboratories must now evaluate different
doses, times, and durations of therapy along and combined with MP, and
at several injury levels. Investigation of all these variable requires
thousands of experiments, beyond the capabilities of any individual
laboratory. Many promising treatments now await such pre-clinical
investigation. Systematic pre-clinical data allow rational design
treatment protocols. Arbitrary treatment protocols have a high risk of
false negatives. A Multicenter Animal Spinal Cord Injury Study (MASCIS) is therefore
proposed. Eight leading SCI laboratories will participate: New York
University, Ohio State University, Washington University, University of
Cincinnati, University of California at San Francisco, Medical University
of South Carolina, Georgetown University, A. I. duPont Institute. Data
analysis will be carried out at Yale University. The centers will use
the same SCI model and outcome measures to study 5 neuroprotective
agents: MP (glucocorticoid), YM-14673 thyrotropin releasing hormone
analog), tirilazad mesylate (a 21-aminosteroid), nalmefene (a kappa-
selective opioid receptor blocker), and excitatory amino acid receptor
blockers. MASCIS will annually examine acute (24h) and chronic (6w) outcomes of
1600 rats subjected to 3 standardized grades of SCI and treated with 2-3
different doses of the drugs started at 0.5h, 6h, or 12h after injury,
continued for 6h or 24h, alone and combined with MP. Plasma and tissue
drug levels will be measured at 2-24h. Acute lesion volumes will be
measured at 24h. Injury conditions will be carefully monitored and
controlled. Acute lesion volumes, behavioral recovery, and different
histologic outcome measures will be compared. This work will provide
detailed and systematic pre-clinical data for acute SCI treatments,
allowing rationale design of treatment protocols. MASCIS is the first
proposal of a multicenter pre-clinical trial on this scale and will
establish a needed precedent for similar studies in stroke and traumatic
brain injury.
StatusFinished
Effective start/end date9/1/938/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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