Development of a database for translational spinal cord injury research.

Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because of the large, heterogeneous data sets involved. In this sense, translational neurological research represents a "big data" problem. In an effort to expedite translation of pre-clinical knowledge into standards of patient care for SCI, we describe the development of a novel database for translational neurotrauma research known as Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI). We present demographics, descriptive statistics, and translational syndromic outcomes derived from our ongoing efforts to build a multi-center, multi-species pre-clinical database for SCI models. We leveraged archived surgical records, postoperative care logs, behavioral outcome measures, and histopathology from approximately 3000 mice, rats, and monkeys from pre-clinical SCI studies published between 1993 and 2013. The majority of animals in the database have measures collected for health monitoring, such as weight loss/gain, heart rate, blood pressure, postoperative monitoring of bladder function and drug/fluid administration, behavioral outcome measures of locomotion, and tissue sparing postmortem. Attempts to align these variables with currently accepted common data elements highlighted the need for more translational outcomes to be identified as clinical endpoints for therapeutic testing. Last, we use syndromic analysis to identify conserved biological mechanisms of recovery after cervical SCI between rats and monkeys that will allow for more-efficient testing of therapeutics that will need to be translated toward future clinical trials.

[1]  Karl Pearson F.R.S. LIII. On lines and planes of closest fit to systems of points in space , 1901 .

[2]  I. Tarlov Spinal cord compression studies. III. Time limits for recovery after gradual compression in dogs. , 1954, A.M.A. archives of neurology and psychiatry.

[3]  I M TARLOV,et al.  Spinal cord compression studies. II. Time limits for recovery after acute compression in dogs. , 1954, A.M.A. archives of neurology and psychiatry.

[4]  C H Tator,et al.  Objective clinical assessment of motor function after experimental spinal cord injury in the rat. , 1977, Journal of neurosurgery.

[5]  J. Wrathall,et al.  Spinal cord contusion in the rat: Production of graded, reproducible, injury groups , 1985, Experimental Neurology.

[6]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[7]  A. Catz,et al.  SCIM – spinal cord independence measure: a new disability scale for patients with spinal cord lesions , 1997, Spinal Cord.

[8]  P. Mccormick Biology of Neurological Recovery and Functional Restoration after Spinal Cord Injury , 1998 .

[9]  Jeffrey D. Scargle,et al.  Publication Bias: The “File-Drawer” Problem in Scientific Inference , 2000 .

[10]  H Barbeau,et al.  Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study , 2000, Spinal Cord.

[11]  John F. Ditunno,et al.  Walking index for spinal cord injury (WISCI II): scale revision. , 2001 .

[12]  K. Anderson Targeting recovery: priorities of the spinal cord-injured population. , 2004, Journal of neurotrauma.

[13]  Aileen J Anderson,et al.  Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. , 2006, Journal of neurotrauma.

[14]  B. Dobkin,et al.  Validity of the Walking Scale for Spinal Cord Injury and Other Domains of Function in a Multicenter Clinical Trial , 2007, Neurorehabilitation and neural repair.

[15]  Juan Lu,et al.  IMPACT database of traumatic brain injury: design and description. , 2007, Journal of neurotrauma.

[16]  Walking index for spinal cord injury (WISCI II): scale revision , 2009, Spinal Cord.

[17]  M. Verrier,et al.  Assessment of the Hand in Tetraplegia Using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) , 2009 .

[18]  A. Faden,et al.  Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. , 2010, Trends in pharmacological sciences.

[19]  Bethann Trapp National Institute of Neurological Disorders and Stroke , 2010 .

[20]  O. Steward,et al.  A bilateral cervical contusion injury model in mice: Assessment of gripping strength as a measure of forelimb motor function , 2010, Experimental Neurology.

[21]  Adam R Ferguson,et al.  A Novel Method for Assessing Proximal and Distal Forelimb Function in the Rat: the Irvine, Beatties and Bresnahan (IBB) Forelimb Scale , 2010, Journal of visualized experiments : JoVE.

[22]  M. S. Read,et al.  United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) , 2011, Spinal Cord.

[23]  Adam R Ferguson,et al.  Syndromics: A Bioinformatics Approach for Neurotrauma Research , 2011, Translational Stroke Research.

[24]  D. J. Cook,et al.  Translating promising preclinical neuroprotective therapies to human stroke trials , 2011, Expert review of cardiovascular therapy.

[25]  W. Tetzlaff,et al.  Rehabilitative training and plasticity following spinal cord injury , 2012, Experimental Neurology.

[26]  Adam R Ferguson,et al.  Methods for Functional Assessment After C7 Spinal Cord Hemisection in the Rhesus Monkey , 2012, Neurorehabilitation and neural repair.

[27]  O. Steward,et al.  Replication and reproducibility in spinal cord injury research , 2012, Experimental Neurology.

[28]  S. Lazic,et al.  A call for transparent reporting to optimize the predictive value of preclinical research , 2012, Nature.

[29]  M. Popovic,et al.  The Graded Redefined Assessment of Strength Sensibility and Prehension: reliability and validity. , 2012, Journal of neurotrauma.

[30]  Adam R. Ferguson,et al.  Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury , 2012, Neurotherapeutics.

[31]  Adam R Ferguson,et al.  Derivation of Multivariate Syndromic Outcome Metrics for Consistent Testing across Multiple Models of Cervical Spinal Cord Injury in Rats , 2013, PloS one.

[32]  D. Lammertse Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture , 2012, Spinal Cord.

[33]  Adam R Ferguson,et al.  Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments. , 2014, Journal of Neurotrauma.

[34]  U. Dirnagl,et al.  Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis. , 2014, JAMA neurology.