Researchers use different ways to analyze gait in animals. Basically we can distinguish two methods: one can either observe or measure gait in an unrestricted manner, or one chooses a forced manner, such as a treadmill or treadwheel.
We all know of animals that are able to regenerate: lizards that grow back their tails, flatworms that can grow into new worms when cut in half. Zebrafish have this special ability as well. You can’t cut them in half and expect two new zebrafish, but there are parts of their body that are able to regenerate, such as heart tissue. The heart cell can divide to replenish missing tissue; interestingly, this property is also shown in a newborn mouse heart, but is lost as the mouse matures (European Biopharmaceutical Review, April issue).
The key to spinal cord injury treatment?
Regenerative abilities may also be the key to spinal cord injury treatment; yet another good reason for scientists to study zebrafish in the lab. They may hold the key to the development of important therapies for spinal cord injury, as Liping Ma and colleagues show us in the April issue of PLOS ONE.
In my last two blogs, I wrote about static gait parameters. Specifically, what a single footprint can tell you and what kind of information you can get from the distance relationships between prints. Now it’s time to talk about all four paws, and the time based relationships between them. If you ask me, we’ve been saving the best blog for last!
Temporal relations are the parameters that have to do with time, such as timing and duration. This is where automation of gait research shows it true colors.
Parameters that describe the relation and distances between footfalls.
Last week I wrote about the value of a print. A footprint, that is. With CatWalk XT, you can extract a lot of information from just one footprint. In this post, I am taking it a step further by talking about the relationship between prints.
In the study of many different disorders that affect the nervous system, muscles, or bones, it is important to know how the animal walks. Does it have a regular gait, following a normal pattern of footsteps? Or can we detect a lack of coordination, or ataxia? Those are important behavioral observations in many studies. So how can you detect them: by looking at the relation between prints.
Gait parameters as behavioral endpoints – parameters from a footprint
So here it is – the first blog in a series of three, about rodent gait analysis and what a single footprint can tell us.
Modern systems – better than ink
So what can one footprint tell you? Well, it could tell you a lot. Simply putting the paw in ink and studying the print left behind is one way to go about it, but there are far more sophisticated ways of footprint analysis. While an ink-print can give you an idea of the print area of a foot, you cannot tell how the animal is distributing his weight across its feet. It also cannot tell you the maximum surface area of a foot touching the ground during the duration of the entire footfall. Modern systems can.
Modern systems that use light to detect a footfall can indicate the intensity of a print, which in turn can correlate with how the animal is bearing its weight. In models of conditions that affect a single limb, the animal often shows less use of the affected paw. This is reflected in a relatively lower intensity of that footprint, which is found in models of arthritis [8,9] and sciatic nerve injury [1,2,4,10].
The usefulness of gait is well established in research on spinal cord injury, ataxia, and arthritis. But in fact, research on all disorders that influence gait in any way, can benefit from gait and footfall analysis. Gait is an important part of the behavioral repertoire of animals, and detailed gait analysis is a logical endpoint to take into account.
The most important tool for the assessment of functional recovery after spinal cord injury in rodents
Stem cell research is a promising area of research for spinal cord injury. With 1,250,000 individuals suffering from chronic spinal cord injury in the US alone, new treatment approaches are necessary and research in this area is not slowing down (Salazar, Uchida, Hamers, Cummings, & Anderson, 2010).
Spinal cord injury typically involves the loss of neurons in the spinal column, which depending on the location of the injury can lead to motor deficits or complete paralysis. Stem cell therapies are a promising area of research for treatment, as stem cells might be able to replace lost neurons and recover some or all motor function.
However, there is a strong lack of consensus about the types of stem cell therapies that might be useful (Schira et al. 2011). This is partially fuelled by inconsistent functional outcomes in studies investigating different therapeutic strategies.
Functional outcomes can also seem more variable due to different tests being applied to assess the success of a therapy. In addition, only using one behavioral test to assess functional recovery can offer an incomplete view of the results, but it is uncommon for more than one test to be used. In contrast, the research done by Schira et al. uses three behavioral tests, one of which is gait and locomotor assessment using CatWalk™ XT.
CatWalk XT provides systematic and extensive automated gait analysis. Measuring a number of dynamic and static gait parameters simultaneously provides a rich insight in functional recovery in response to treatments like stem cell transplantation. Shira et al. showed that stem cells transplanted to the area of injury accumulated within the lesion area, reducing the size of the lesion. Axon regrowth was enhanced, but more importantly, behavioral tasks showed improved locomotor function. Although biologically we can assess whether stem cells seem to be responsive after being translated into the lesioned area, nothing but behavioral testing can evaluate functional recovery. Ultimately, biological assessments can only hint at what we belief the functional outcome might be. For example, differentiation from umbilical cord-derived stem cells continues to be debated. However, effects from transplanting human umbilical cord blood in spinal cord injury have been supported whether differentiation was observed or not. Whether or not neural differentiation is observed, there could be regeneration through (unknown) mechanisms other than differentiation. This is where behavioral assessment provides most illuminating insights into the viability of therapeutic targets.
Ultimately, the functional outcome is what matters, even if the underlying mechanisms require further study.