The Histopathology of Severe Graded Compression in Lower Thoracic Spinal Cord Segment of Rat, Evaluated at Late Post-injury Phase

Jana Fedorova,Katarina Bimbova,Jaroslav Pavel,Erika Kellerova

doi:10.1007/s10571-021-01139-7

Jana Fedorova, Katarina Bimbova + Show 2 more

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https://doi.org/10.1007/s10571-021-01139-7

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Abstract

Spontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

Highlights

Despite the many experimentally promising therapeutic approaches invented in recent decades, there is no reliable, effective and clinically accepted treatment currently available for disabled patients after spinal cord injury (SCI)
The improvement of locomotor function after 40 g and 50 g compression was more moderate and stabilized at 8.8 and 8.1 points, which correlates to sweeping without weight support
Since it was demonstrated that a 20 g compression lasting 20 or even 40 min did not induce a severe and long-term impairment of hind limb function (Hamamoto et al 2007), we started our experimental compression at a 30 g weight

Summary

Introduction

Despite the many experimentally promising therapeutic approaches invented in recent decades, there is no reliable, effective and clinically accepted treatment currently available for disabled patients after spinal cord injury (SCI). A wide range of SCI models are used to gain a detailed understanding of the complexity of human SCIs and to investigate the efficacy of possible therapeutic interventions under controlled conditions in terms of the animal utilized, spinal cord segmental level and injury mechanisms. The cervical region is most commonly injured in human SCIs, a systematic review of relevant literature revealed that approximately 81% of experimental SCIs are performed at the thoracic spinal level (Sharif-Alhoseini et al 2017) probably for reasons of feasibility and animal welfare. Most human SCIs are caused by compression or contusion of the spinal cord (Anwar et al 2016); these type of injuries are considered as relevant and commonly used models in experimental studies (Alizadeh et al 2019). Whereas contusion causes an acute and transient injury to the spinal cord, a compression injury is characterized by spinal cord compression over

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