Lizard tail spinal cord: a new experimental model of spinal cord injury without limb paralysis

Abstract

Spinal cord injury (SCI) is a well-known devastating lesion that sadly is very resistant to all treatment attempts. This fact has stimulated the exploration of multiple regenerative strategies that are examined at both the basic and clinical level. For laboratory research, different in vivo models are used, but each has many important limitations. The main limitation of these models is the high level of animal suffering related to the inflicted neurologic injury. It has caused a growing tendency to limit the injury, but this, in turn, produces incomplete SCI models and uncertainties in the neuroregeneration interpretation. To overcome such limitations, a new experimental SCI model is proposed. Geckos have been extensively examined as a potential animal model of SCI. Their spinal cord extends into the tail and can be transected without causing the typical neurologic consequences observed in rat models. In this study, we compared the gecko tail SCI model with the rat model of thoracic SCI. Anatomic and histologic analyses showed comparability between the gecko and rat in diameter of spinal canal and spinal cord, as well as applicability of multiple staining techniques (hematoxylin and eosin, immunostaining, and scanning and transmission electron microscopy). We tested the suitability of in vivo study with 3 prototype implants for the reconstruction of SCI: a multichannel sponge, a multilaminar tube, and a gel cylinder. These were compared with a spinal cord excision (control). A 20-wk observation revealed no adverse effects of SCI on the animals' well-being. The animals were easily housed and observed. Histologic analysis showed growth of nervous tissue elements on implant surface and implant cellular colonization. The study showed that the gecko SCI model can be used as a primary model for the assessment of SCI treatment methods. It provides a platform for testing multiple solutions with limited animal suffering before performing tests on mammals. Detailed results of the experimental conditions and testing techniques are provided.-Szarek, D., Marycz, K., Lis, A., Zawada, Z., Tabakow, P., Laska, J., Jarmundowicz, W. Spinal cord injury (SCI) is a lesion that has a relatively high incidence (1) and is characterized by high resistance to any restorative treatment. Multiple experimental, laboratory, and clinical investigations are conducted in an attempt to understand the mechanisms underlying this trauma and to identify potential treatment options. Studies are performed in in vitro and in vivo models that have both pros and cons. In vitro studies are relatively easy to perform and repeat; they do not require animal euthanasia and can be performed in large numbers. The disadvantage of this type of study is a relatively short observation time and examination limited to 1 or 2 different cell lines during 1 test. Moreover, they do not provide data on how the whole organism may respond to the study drug, implant, or experimental condition. On the other hand, in vivo studies provide information on how multiple tiss...

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

“…Ultimately, these species restore damaged or lost tissue with a replacement that closely resembles the original organ in both structure and function. Among amniotes, only lizards appear to be capable of spontaneous spinal cord regeneration, and only within the tail (Alibardi & Miolo, ; McLean & Vickaryous, ; Szarek et al, ; Whimster, ). In stark contrast with non‐amniotes, the regenerated spinal cord of lizards—while functional—is morphologically distinct from that of the original.…”

“…Here we provide the first detailed investigation of lizard ELCs prior to and following spinal cord injury. The model for our studies is the leopard gecko (Eublepharis macularius; hereafter 'gecko'), a captive-bred and lab-amenable lizard (Delorme, Lungu, & Vickaryous, 2012;McLean & Vickaryous, 2011;Szarek et al, 2016;Whimster, 1978). As for many lizards, geckos are able to self-detach the tail and then regenerate a replacement (Delorme et al, 2012;McLean & Vickaryous, 2011).…”

Potential Involvement of Snail Members in Neuronal Survival and Astrocytic Migration during the Gecko Spinal Cord Regeneration

“…(Wang et al, 2012; Zhou et al, 2013; Bai et al, 2015; Liu et al, 2015). The animal is becoming a new experimental model in the investigation of spinal cord regeneration (Szarek et al, 2016). The regenerating spinal cord (ependymal tube) begins to penetrate into the blastema at 10–15 days after tail amputation (McLean and Vickaryous, 2011; Delorme et al, 2012).…”

“…Unlike mammals, the regenerative model organisms including fish, amphibian and several reptiles are capable of regenerating spinal cord throughout their lifespan after injury (Dong et al, 2013; Lee-Liu et al, 2013; Szarek et al, 2016; Rasmussen and Sagasti, 2017). Spinal cord injury (SCI) by transection, resection, compression or tail amputation in these animals, will results in a robust ability to regrow axons, repair circuits and recover function (Díaz-Quiroz and Echeverri, 2013).…”

Tail regeneration and other phenomena of wound healing and tissue restoration in lizards

“…A second advantage of using lizards in regeneration research is that tissues of the tail (including blood vessels, lymphatics and the spinal cord) can be easily accessed, manipulated and studied in vivo, with minimal consequence to the remainder of the body. For example, the spinal cord of the tailwhich closely resembles that of the mammalian bodycan be transected and experimentally altered without the risk of limb paralysis or incontinence (Whimster, 1978;Szarek et al, 2016). Similarly, the lizard tail has been used as a novel platform to investigate lymphangiogenesis without impairing lymphatic drainage to the body core or limbs (Daniels et al, 2003;Blacker et al, 2007).…”