Johana Bastidas1, Megan R. Detloff2, Linda Jones3, Marco Baptista3,Karim Fouad4, Taleen Hanania1.
1 Psychogenics, Paramus, New Jersey, US 2Department of Neurobiology & Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, US, 3Christopher & Dana Reeve Foundation, Short Hills, New Jersey, US4 University of Alberta, Department of Physical Therapy, Edmonton, Alberta, CA.
Spinal cord injury (SCI) is a neurological condition with a devastating impact on the quality of life of affected individuals, resulting in altered motor, sensory function and autonomic function. Valid, reliable and consistent SCI preclinical models are indispensable tools for advancing novel therapeutics to improve outcomes following.
In collaboration with the Christopher &Dana Reeve Foundation, PsychoGenics validated a graded thoracic (T8) SCI contusion lesion model in female Sprague Dawley rats, employing a clinically relevant controlled lesion method (IH impactor) to produce four graded lesion severities. Rats underwent laminectomy followed by contusion SCI using impact forces of 170, 200, 250 Kdyn, or 250 Kdyn with a 3-second dwell time. Functional recovery was assessed over five weeks using standard locomotor tests: Basso, Beattie, Bresnahan locomotor rating scale – BBB (Basso, Beattie, Bresnahan 1995), horizontal ladder test (Metz and Wishaw, 2009) and PsychoGenics’ proprietary gait analysis system, NeuroCube®. Changes in mechanical and thermal sensation were evaluated using von Frey (Detloff et al. 2012) and Hargreaves’ tests. Parameters such as time for bladder function recovery, urinary/health complications, and body weights were also recorded overtime.
The severity of SCI correlated with biomechanical values recorded at the time of impact, as well as behavioral and histological parameters (lesion size, spared tissue). Remarkably, locomotor behavioral assessments demonstrated sensitivity in detecting lesions with differences as low as 30-50 Kdyn. Distinct patterns of locomotor recovery were observed across the four groups, with significant differences noted between injury severities based on BBB and ladder test. Hypersensitivity to mechanical stimuli was evident post-SCI when compared with baseline values and/or sham animals. Rats subjected to the most severe lesion (250Kdyn + 3 seconds dwell time) exhibited the most consistent and significant changes in sensation and bladder function. Thus, we have developed an in vivo SCI platform to assess efficacy of potential therapeutic interventions that encompasses comprehensive evaluations of general health, locomotion, and sensation.
References:
Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995 Vol. 12 Issue 1 Pages 1-21. doi: 10.1089/neu.1995.12.1.
Metz GA, Whishaw IQ. The ladder rung walking task: a scoring system and its practical application. J Vis Exp 2009;28), doi:10.3791/1204.
Detloff MR, Fisher LC, Deibert RJ, Basso DM. Acute and chronic tactile sensory testing after spinal cord injury in rats. J Vis Exp. 2012 Apr 4;(62):e3247. doi: 10.3791/3247.
Support: This work was supported by the Christopher & Dana Reeve Foundation and Psychogenics.