Neuropeptides in spinal cord injury: Comparative experimental models

Due to an ever-growing population of individuals with chronic spinal cord injury, there is a need for experimental models to translate efficacious regenerative and reparative acute therapies to chronic injury application. The present study assessed the ability of fluid grafts of either Schwann cells (SCs) or olfactory ensheathing glia (OEG) to facilitate the growth of supraspinal and afferent axons and promote restitution of hind limb function after transplantation into a 2-month-old, moderate, thoracic (T8) contusion in the rat. The use of cultured glial cells, transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP), permitted long-term tracking of the cells following spinal cord transplantation to examine their survival, migration, and axonal association. At 3 months following grafting of 2 million SCs or OEG in 6 μl of DMEM/F12 medium into the injury site, stereological quantification of the three-dimensional reconstructed spinal cords revealed that an average of 17.1 ± 6.8% of the SCs and 2.3 ± 1.4% of the OEG survived from the number transplanted. In the OEG grafted spinal cord, a limited number of glia were unable to prevent central cavitation and were found in patches around the cavity rim. The transplanted SCs, however, formed a substantive graft within the injury site capable of supporting the ingrowth of numerous, densely packed neurofilament-positive axons. The SC grafts were able to support growth of both ascending calcitonin gene-related peptide (CGRP)-positive and supraspinal serotonergic axons and, although no biotinylated dextran amine (BDA)-traced corticospinal axons were present within the center of the grafts, the SC transplants significantly increased corticospinal axon numbers immediately rostral to the injury–graft site compared with injury-only controls. Moreover, SC grafted animals demonstrated modest, though significant, improvements in open field locomotion and exhibited less foot position errors (base of support and foot rotation). Whereas these results demonstrate that SC grafts survive, support axon growth, and can improve functional outcome after chronic contusive spinal cord injury, further development of OEG grafting procedures in this model and putative combination strategies with SC grafts need to be further explored to produce substantial improvements in axon growth and function.

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Experimental Models of Spinal Cord Injury in Laboratory Rats

Acta Naturae ◽

10.32607/20758251-2018-10-3-4-10 ◽

2018 ◽

Vol 10 (3) ◽

pp. 4-10 ◽

Cited By ~ 3

Author(s):

A. N. Minakov ◽

A. S. Chernov ◽

D. S. Asutin ◽

N. A. Konovalov ◽

G. B. Telegin

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Experimental Studies ◽

Therapeutic Agents ◽

Experimental Models ◽

Biodegradable Materials ◽

Topical Issue ◽

Laboratory Rats ◽

Advantages And Disadvantages ◽

Cord Injury

Pathologies associated with spinal cord injury are some of the leading diseases in the world. The search for new therapeutic agents and 3D biodegradable materials for the recovery of spinal cord functions is a topical issue. In this review, we have summarized the literature data on the most common experimental models of spinal cord injury in laboratory rats and analyzed the experience of using 3D biodegradable materials (scaffolds) in experimental studies of spinal trauma. The advantages and disadvantages of the described models are systematically analyzed in this review.

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In vivo and in vitro models of traumatic injuries of the spinal cord

Cell and Organ Transplantology ◽

10.22494/cot.v5i1.71 ◽

2017 ◽

Vol 5 (1) ◽

pp. 87-93

Author(s):

O. Rybachuk ◽

I. Arkhypchuk ◽

Yu. Lazarenko

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Traffic Accidents ◽

Experimental Models ◽

The Body ◽

Nerve Tissue ◽

Economic Losses ◽

Cord Injury

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.

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Experimental Model of Spinal Cord Injury (SCI) in rats: management guidelines

Coluna/Columna ◽

10.1590/s1808-18512013000100015 ◽

2013 ◽

Vol 12 (1) ◽

pp. 70-72 ◽

Cited By ~ 4

Author(s):

Asdrubal Falavigna ◽

Fernanda Cechetti ◽

Guilherme Finger ◽

Leonardo Gilmone Ruschel ◽

Grasiela Marcon ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Postoperative Management ◽

Experimental Models ◽

New Drugs ◽

Laboratory Animals ◽

Standard Protocol ◽

New Techniques ◽

Management Guidelines ◽

Cord Injury

Surgical experiments with laboratory animals are necessary for medical research. These studies aim to clarify the mechanism of disease, investigate the action and efficacy of new drugs or biological markers, as well as develop and enhance new therapies and apply new techniques. Regarding the models of spinal cord injury (SCI), there are several different methods that address the handling of the animals, especially concerning the use of analgesics, antibiotics and pre- and postoperative management. The lack of uniformity and standardization among the studies does not allow the understanding of the model of SCI or the proper handling of the paraplegic animals, hampering the adequate interpretation and comparison of results. The goal of this study is to establish a standard protocol on the handling of animals subjected to experimental models of SCI.

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Cellular Transplantation and Spinal Cord Injury

Neurosurgery ◽

10.1097/00006123-200009000-00033 ◽

2000 ◽

Vol 47 (3) ◽

pp. 691-700 ◽

Cited By ~ 3

Author(s):

Kaveh Barami ◽

Fernando G. Diaz

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cell Types ◽

Experimental Models ◽

General Strategy ◽

Functional Connection ◽

Alternative Pathways ◽

Technological Advances ◽

Cellular Transplantation ◽

Cord Injury

ABSTRACT SPINAL CORD INJURY is often characterized by immediate and irreversible loss of sensory and motor functions below the level of injury. Cellular transplantation in various experimental models of spinal cord injury has been used as a strategy for reducing deficits and improving functional recovery. The general strategy has been aimed at promoting regeneration of intrinsic injured axons with the development of alternative pathways that facilitate a partial functional connection. Other objectives of cellular transplantation studies have included replacement of lost cellular elements, alleviation of chronic pain, and modulation of the inflammatory response after injury. This review focuses on the cell types that have been used in spinal cord transplantation studies in the context of evolving biological perspectives, technological advances, and new therapeutic strategies and serves as a point of reference for future studies.

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Rat Spinal Cord Injury Experimental Model

Folia Veterinaria ◽

10.1515/fv-2016-0017 ◽

2016 ◽

Vol 60 (2) ◽

pp. 41-46 ◽

Cited By ~ 2

Author(s):

I. Šulla ◽

V. Balik ◽

J. Petrovičová ◽

V. Almášiová ◽

K. Holovská ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Spinal Cord Injuries ◽

Basic Research ◽

Experimental Models ◽

Neurological Deficits ◽

Survival Times ◽

Cord Injury ◽

Female Wistar Rats ◽

Trauma Model

Abstract 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 their motor functions were assessed by the Basso, Beattie, Bresnahan (BBB) test 6 hours, 7, 21 and 28 days after the simulated SCI. All 23 rats survived the surgical procedures. The control rats were without any neurological deficits. There were, in every experimental subgroup, 1 or 2 rats with extreme BBB scores. So the rats with the maximum and minimum BBB values were excluded. Then, the results acquired in the residual 5 rats in each group were averaged and statistically analysed by the Tukey multiple comparisons test. Statistically significant intersubgroup differences were found at all survival times equal to or longer than 7 post SCI days. The goal of the SCI experiment was to generate a reproducible and reliable, submaximal spinal cord trauma model. The statistical analyses demonstrated that this objective was best achieved in the subgroup-2 with the 40 g compression.

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BAMOS: A recording application for BAsso MOuse scale of locomotion in experimental models of spinal cord injury

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2018.02.021 ◽

2018 ◽

Vol 96 ◽

pp. 32-40

Author(s):

Alberto Gómez ◽

Manuel Nieto-Díaz ◽

Ángela del Águila ◽

Enrique Arias

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Experimental Models ◽

Cord Injury

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Microglia limit lesion expansion and promote functional recovery after spinal cord injury in mice

10.1101/410258 ◽

2018 ◽

Cited By ~ 1

Author(s):

Faith H. Brennan ◽

Jodie C.E. Hall ◽

Zhen Guan ◽

Phillip G. Popovich

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Recovery ◽

Spontaneous Recovery ◽

Recovery Of Function ◽

Experimental Models ◽

Post Injury ◽

Thoracic Spinal ◽

Cord Injury

AbstractTraumatic spinal cord injury (SCI) elicits a robust intraspinal inflammatory reaction that is dominated by at least two major subpopulations of macrophages, i.e., those derived from resident microglia and another from monocytes that infiltrate the injury site from the circulation. Previously, we implicated monocyte-derived macrophages (MDMs) as effectors of acute post-injury pathology after SCI; however, it is still unclear whether microglia also contribute to lesion pathology. Assigning distinct functional roles to microglia and MDMs in vivo has been difficult because these CNS macrophage subsets are morphologically and phenotypically similar. Here, to characterize the role that microglia play in experimental models of thoracic spinal contusion or lumbar crush injury, mice were fed vehicle chow or chow laced with a CSF1R receptor antagonist, PLX5622. Feeding PLX5622 depletes microglia. In both groups, spontaneous recovery of hindlimb motor function was evaluated for up to 8 weeks post-SCI using open-field and horizontal ladder tests. Histopathological assessment of intraspinal pathology was assessed in 8 week post-injury tissues. In both SCI models, microglia depletion exacerbated lesion pathology and impaired spontaneous recovery of hind limb function. Notably, the loss of microglia prevented astroglial encapsulation of the lesion core, which was associated with larger lesions, enhanced demyelination and neuron loss and a larger inflammatory response that was dominated by monocyte-derived macrophages. The neuroprotective and healing properties of microglia become obvious in the subacute phases of recovery; microglia depletion up to 7 days post-injury (dpi) had no apparent effect on recovery while delayed depletion from 8-28dpi exacerbated lesion pathology and significantly impaired functional recovery. These data suggest that microglia have essential tissue repair functions after SCI. Selective enhancement of microglial activities may be a novel strategy to preserve tissue and promote recovery of function after neurotrauma.

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