The Staircase Test in Mice After Spinal Cord Injury
Weihong Pan1, Abba J. Kastin1, Chaim G. Pick2
1
Pennington Biomedical Research Center,
Baton Rouge,
Louisiana,
USA
2
Department of Anatomy and Anthropology,
Sackler Faculty of Medicine,
Tel Aviv University,
Israel
Received 7 August 2004; received in revised form 14 September 2004,; accepted 19 September 2004
Correspondence and requests for reprints should be addressed to:
Weihong Pan, M.D., Ph.D.
PBRC
6400 Perkins Road
Baton Rouge, LA 70808
Tel. 1-225-763-2707
Fax 1-225-763-0261
weihong.pan@pbrc.edu
Abstract
Objectives
Although spinal cord injury (SCI) of the rat by contusion is the prevalent model, for mouse models of SCI to gain wider acceptance one of the challenges has been to design an accurate test battery for assessment of functional recovery.
Methodology
In this study, we compared two mouse models of SCI - complete transection and compression in the upper lumbar region.
Results
The open-field locomotor behavioral score was insensitive to changes during the first few days after SCI. The staircase test, however, showed that transected mice performed significantly better than the compression group by 3 d after injury. Despite the improvement in locomotor behavior within the first week, all mice showed a persistent deficit in pain/temperature sensation measured by hotplate and tail flick tests. Since tumor necrosis factor (TNF)a is involved in hyperalgesia and can cross the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) by receptor-mediated transport, we further determined whether blood-borne TNFa plays a role in the behavioral changes. To do this, we compared the time- and spatial-patterns of TNFa permeation with that of BSCB disruption. Compression SCI caused a greater disruption of the BSCB than transection. The barrier disruption, represented by increased spinal cord uptake of radioactively labeled albumin, was present at the time points immediately and 3 d after SCI in the compression model, but only immediately after SCI in the transection model. By contrast, the increased entry of TNFa from blood to spinal cord was present both immediately and 3 d after SCI in both models.
Conclusion
Since it was possible that peripheral TNFa contributed to the sensory deficit in SCI mice, the staircase test proved useful for the detection of subtle improvement in locomotor function. This test showed that early functional recovery was not impeded by the upregulated TNFa transport across the BSCB.
Key Words
Staircase test; Blood-spinal cord barrier; Transport; TNFa; Neuroregeneration; Spinal cord injury
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