Experimental Laceration Spinal Cord Injury Model (original) (raw)
Related papers
In vivo and in vitro models of traumatic injuries of the spinal cord
In recent years, there is a growing interest in the mechanisms of regeneration of damaged nerve tissue, including the spinal cord, as its injuries are quite common due to traffic accidents, industrial injuries and military actions. Damage to the spinal cord results in the loss of functional activity of the body below the injury site, which affects person's ability to self-service and significantly reduces its efficiency. The effects of spinal injuries annually cause significant social and economic losses worldwide, including Ukraine. The development of new treatments for pathologies of the central nervous system requires mandatory pre-testing of their effectiveness in experiments in vitro and in vivo. Therefore, searching and creation of optimal animal model of spinal cord injury is in order to it meets most complete picture of the damage characteristic of real conditions in humans. This is an important task of modern neurophysiology. Such models can be used, primarily, for a more detailed clarification of the pathogenesis of all levels of nerve tissue damage and research of its own recovery potential by endogenous reparation mechanisms. In addition, experimental models allow to estimate the safety and predict the effectiveness of various therapeutic approaches to spinal cord injury. The first priority in treating this pathological process is to create conditions for regenerative growth of injured nerve fibers through the injured area of the spinal cord or spinal nerves. Solving of this problem is possible by means of tissue neuroengineering involving replacement of natural tissue environment with synthetic matrix, stimulation and support of axonal regeneration growth and their myelination. In this review, we systematically examine various options for spinal cord injury in rodents, which are the most available models for research and often used in experiments. Simultaneously we analyze the advantages and disadvantages of such models. We are focused on injuries of the thoracic division of the spinal cord, since they are most common in research and less deadly to laboratory animals [3]. The thoracic spine is more affordable to trauma modelling than lumbar, due to greater volume of epidural space, which makes the injury easier to perform, and it becomes possible to study the processes of functional recovery of neural tissue. From pathogenic point of view on a spinal cord trauma, there are primary damaging factors, secondary pathological reactions and chronic processes. The most important primary factor of SC injury while mechanical damaging is its compression by displaced parts of vertebrae. Necrosis of central gray matter occurs within four hours after the injury. Degeneration of neurons and their processes appear in around 8 hours The effects of spinal injuries annually cause significant social as well as economic losses in all countries including Ukraine. Spinal cord injury in most cases is accompanied by considerable disability that creates an additional budgetary pressure. Among these patients, 80 % are men of working age. In addition to industrial and domestic accidents, a number of such cases is growing in conditions of military action. Considerable attention among the neurobiological and neuro-physiological communities is focused on the findings the most adequate and integrated models of spinal cord (SC) injury, similar to spinal trauma in humans. However, models of complex injuries of the spine and spinal cord are accompanied by high mortality among the animals. In this regard, models that reproduce the individual pathogenesis of SC injury are being developed, although its pathogenetic stage remains a complex and multifactorial process. Therefore, proper selection of the model system to establish the molecular and cellular mechanisms of spinal cord injury is the key to a better understanding of the problem in clinic. The consequences of spinal injury cannot be completely overcome by the regenerative potential of endogenous neural tissue. They evolve over time and manifest severe complications years after the injury [1, 2]. Therefore, the selection of adequate animal model of spinal cord injury in experimental condition will provide more detailed analysis of the trauma effects and choose the best options for improvement of damaged neural tissue.
In Vitro Models of Spinal Cord Injury
Recovery of Motor Function Following Spinal Cord Injury, 2016
Living organisms are extremely complex functional systems. At present, there are many in vivo models of spinal cord injury (SCI) that allow the modeling of any type of central nervous system (CNS) injury, however, with some disadvantages. The production of injury models can be a highly invasive and time-consuming process and requires high technical requirements, and costly financial issues should also be taken into account. Of course, a large number of animals have been used to obtain the relevant data of statistical significance. All of these aspects can be reduced by carrying out experiments in in vitro conditions. The primary advantage of in vitro method is that it simplifies the system under study. There are two major groups of in vitro model in use: cell culture and organotypic slice (OTS) culture. OTS is an intermediate system of the screening of in vitro cell culture and animal models and represents the in vitro system preserving the basic tissue architecture that able to closely mimic the cellular and physiological characteristics in vivo. In vitro models are the preferred methods for the study of acute or subacute pathophysiology after a trauma stimulus, enabling precise control on the extracellular environment, easy and repeatable access to the cells.
Journal of Neuroscience Methods, 2009
Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance, and significantly impacts life expectancy and quality. Animal models provide a good opportunity to test therapeutic strategies in vivo. C57BL/6 mice were subjected to laminectomy at T9 and compression with a vascular clip (30 g force, 1 min). Two groups were analyzed: injured group (SCI, n = 33) and laminectomy only (Sham, n = 15). Locomotor behavior (Basso mouse scale-BMS and global mobility) was assessed weekly. Morphological analyses were performed by LM and EM. The Sham group did not show any morphofunctional alteration. All SCI animals showed flaccid paralysis 24 h after injury, with subsequent improvement. The BMS score of the SCI group improved until the intermediate phase (2.037 ± 1.198); the Sham animals maintained the highest BMS score (8.981 ± 0.056), p < 0.001 during the entire time. The locomotor speed was slower in the SCI animals (5.581 ± 0.871) than in the Sham animals (15.80 ± 1.166), p < 0.001. Morphological analysis of the SCI group showed, in the acute phase, edema, hemorrhage, multiple cavities, fiber degeneration, cell death and demyelination. In the chronic phase we observed glial scarring, neuron death, and remyelination of spared axons by oligodendrocytes and Schwann cells. In conclusion, we established a simple, reliable, and inexpensive clip compression model in mice, with functional and morphological reproducibility and good validity. The availability of producing reliable injuries with appropriate outcome measures represents great potential for studies involving cellular mechanisms of primary injury and repair after traumatic SCI.
Advances in three-dimensional reconstruction of the experimental spinal cord injury
Computerized Medical Imaging and Graphics, 2000
Three-dimensional (3D) computer reconstruction is an ideal tool for evaluating the centralized pathology of mammalian spinal cord injury (SCI) where multiple anatomical features are embedded within each other. Here, we evaluate three different reconstruction algorithms to three-dimensionally visualize SCIs. We also show for the first time, that determination of the volume and surface area of pathological features is possible using the reconstructed 3D images themselves. We compare these measurements to those calculated by older morphometric approaches. Finally, we demonstrate dynamic navigation into a 3D spinal cord reconstruction. ᭧ . He has served on numerous executive boards and review panels for both private foundations and the federal government. His Center's research and the development of treatments for spinal injury have received national and international attention in both the printed media (Discover Magazine, The New Scientist, Time Magazine) and broadcast media (NBC Dateline, NBC Today Show, PBS, NPR).
A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice
Journal of visualized experiments : JoVE, 2017
Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10(th) thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.
Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies
Biomaterials, 2004
Tissue engineering approaches to spinal cord injury (SCI) treatment are attractive because they allow for manipulation of native regeneration processes involved in restoration of the integrity and function of damaged tissue. A clinically relevant spinal cord regeneration animal model requires that the model mimics specific pathologic processes that occur in human SCI. This manuscript discusses issues related to preclinical testing of tissue engineering spinal cord regeneration strategies from a number of perspectives. This discussion includes diverse causes, pathology and functional consequences of human SCI, general and species related considerations, technical and animal care considerations, and data analysis methods.
Journal of Neurotrauma, 2009
To study the pathophysiology of spinal cord injury (SCI), we used the LISA-Vibraknife to generate a precise and reproducible dorsal laceration SCI in the mouse. The surgical procedure involved a T9 laminectomy, dural resection, and a spinal cord laceration to a precisely controlled depth. Four dorsal hemisection injuries with lesion depths of 0.5, 0.8, 1.1, and 1.4 mm, as well as normal, sham (laminectomy and dural removal only), and transection controls were examined. Assessments including the Basso Mouse Scale (BMS), footprint analysis, beam walk, toe spread reflex, Hargreaves' test, and transcranial magnetic motor-evoked potential (tcMMEP) analysis were performed to assess motor, sensorimotor, and sensory function. These outcome measures demonstrated significant increases in functional deficits as the depth of the lesion increased, and significant behavioral recovery was observed in the groups over time. Quantitative histological examination showed significant differences between the injury groups and insignificant lesion depth variance within each of the groups. Statistically significant differences were additionally found in the amount of ventral spared tissue at the lesion site between the injury groups. This novel, graded, reproducible laceration SCI model can be used in future studies to look more closely at underlying mechanisms that lead to functional deficits following SCI, as well as to determine the efficacy of therapeutic intervention strategies in the injury and recovery processes following SCI.
Modeling of Post Traumatic Glial Scar after ControlledCryodestruction of Rat Spinal Cord
2020
Spinal cord injury (SCI) represents a relevant problem under both clinical e social points of view. Post traumatic glial scarring is recognized as one of the main factors which would affect negatively axons regrowth following SCI. As in the situation of SCI occurring in humans, presently available animal experimental model of SCI provoke a wide range of glial scarring reaction as a result of trauma, thus investigating the specific issue of post traumatic glial scarring would require an extremely high number of animal due to significant inter animals variability. We recently introduced a new model of experimental SCI in rats where a controlled unilateral cryo-induced lesion was created. Sprague-Dawley rats of adequate size were used, microsurgical unilateral exposure of lower thoracic spinal cord dura was performed, and cryolesion was induced via a controlled exposure to -20° temperature for one minute using liquid azote. The animals were sacrificed following 30 days of close observa...
Rat Spinal Cord Injury Experimental Model
Folia Veterinaria, 2016
Spinal cord injuries (SCI) with their tragic consequences belong to the most serious pathological conditions. That is why they have stimulated basic research workers, as well as health care practitioners, to search for an effective treatment for decades. Animal experimental models have been essential in these efforts. We have jointly decided to test and standardize one of the spinal cord injury compression models in rats. Twentythree adult female Wistar rats weighing 250-320 g were utilized. Employing general anaesthesia along with a mixture of sevoflurane with O2, 2 rats (sham controls) had their vertebral arch of either Th8 or Th9 vertebra removed (laminectomy). The other 21 experimental rats with similar laminectomies were divided into 3 subgroups (n = 7) which received compression impact forces of 30, 40 or 50 g (subgroups-1, -2, and -3, respectively) applied on their exposed spinal medulla for 15 minutes. All rats were observed for 28 days after the experimental procedure and t...