Functional testing in animal models of spinal cord injury: not as straight forward as one would think

Abstract

When exploring potential treatments for spinal cord injury (SCI), functional recovery is deemed the most relevant outcome measure when it comes to translational considerations. Yet, assessing such recovery and potential treatment effects is challenging and the pitfalls are frequently underestimated. The consequences are that in many cases positive results cannot be reliably replicated, and likely treatments that appear to lack effects have been dismissed prematurely. In this article we review the relationships between lesion location/severity and functional outcomes with specific consideration given to floor and ceiling effects. The roles of compensatory strategies, the challenges of distinguishing them from bona fide recovery, and of comparing function to pre-injury levels given the variability inherent in animal testing are discussed. Ultimately, we offer a series of considerations to enhance the power of functional analysis in animal models of SCI.

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

“…On the other hand, hemisection is a case of partial lesion with a high rate of spontaneous recovery and a high risk of inconsistencies in the injuries from one animal to the next, which might lead to misinterpretation of the behavioral evaluation. 35,36 Further investigation using a subacute or chronic compression SCI model together with systematic functional evaluation is, therefore, the next step in establishing the link between in vivo biological properties of the ECM hydrogel in acute and chronic SCI.…”

An automated rat single pellet reaching system with high-speed video capture

“…Manpower requirements, as well as difficulty isolating reaching apparatuses, limit the number of animals that can be trained and the number of trials per session. This degree of investigator involvement also introduces variability between training sessions, and likely contributes to variability in results between (and even within) labs (Fouad et al, 2013). Further variability in training can occur due to variations between laboratory conditions, training protocols, behavioral testing apparatuses, rodent strains, and ages.…”

Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats

“…11,13,[75][76][77][78] Whereas some evidence has been reported suggesting that collateral sprouting of intact descending motor fibers may not contribute to recovery of forelimb motor function, there is also compelling evidence that under certain conditions, such potential does exist. 11,13,76,79 Alternatively, we cannot rule out the possibility that PRV is not able to transsynaptically label the new synapses formed in response to SCI, although this would seem unlikely based on what is known about the viral transport. Another consideration regarding the absence of robust differences in interneuronal labeling observed after SCI may be related to the PRV tracing methods employed in this study.…”

“…79 One of the major issues is how to characterize and evaluate the contribution of compensatory behaviors to motor recovery. One approach is to use qualitative assessments such as the FLS, the BBBm or the ''atypical behaviors'' component of the vermicelli pasta test.…”