Johana Bastidas, Megan R. Detloff, Linda Jones-Norse, Marco Baptista, Taleen Hanania.
2Department of Neurobiology & Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, PA 19129
Spinal cord injury (SCI) is a neurological condition with a devastating impact on the quality of life of affected individuals. Despite current medical care advancements, individuals with SCI may endure decreased motor function, altered sensation, and a myriad of autonomic changes for many years following the initial injury. Valid, reliable and consistent SCI preclinical models are indispensable tools for advancing novel therapeutics that are both safe and effective in improving SCI outcomes.
In collaboration with the Christopher and 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 (BBB locomotor rating scale, horizontal ladder test), and PsychoGenics’ proprietary gait analysis system, NeuroCube®. Changes in mechanical and thermal sensation were evaluated using von Frey and Hargreaves’ tests. Notably, 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 with 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 performance. 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, as well as bladder function. Thus, we have developed an in vivo SCI platform to assess the efficacy of potential therapeutic interventions that encompasses comprehensive evaluations of general health, locomotion, and sensation.