Corticosteroids Reduce Glial Fibrillary Acidic Protein Expression in Response to Spinal Cord Injury in a Fetal Rat Model of Dysraphism

Abstract

Background: Exposure of the spinal cord in myelomeningocele (MM) throughout gestation increases spinal injury. Astrocyte activation evidenced by glial fibrillary acidic proteins (GFAP) indicates the extent of injury. Corticosteroids modulate GFAP synthesis, but their effect in MM is unclear. The purpose of this study was to evaluate the GFAP expression in a fetal rat model of dysraphism and the effect of corticosteroid treatment on this marker and on clinical neurological disabilities. Methods: Dysraphism was surgically created in 2 groups of 48 rat fetuses; group 1: control, and group 2: treated with corticosteroid. Each group was subdivided into fetuses with surgically created MM, controls and shams on day 18.5 of gestation (term = 22 days). Fetuses were harvested on day 21.5, examined for evidence of neurological deficits, and the following clinical parameters were registered: kyphosis, tail deformities, leg deformities, leg paralysis or paresis and pain perception. The fetuses were fixed for GFAP immunostaining. Results: All fetuses with MM in group 1 presented neurological deficits and glial reactions with GFAP expression, as opposed to controls and shams. In group 2, corticosteroid treatment prevented some neurological deficits (18–25%), reducing glial response and GFAP expression. Conclusions: Experimentally induced dysraphism in the rat fetus is related to glial response and increased GFAP expression in the spinal cord. Corticoid treatment clinically improved nerve injury in some fetuses. It reduced glial reaction and GFAP expression.

CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida

“…In this RA-induced rat model, the most common neuropathological feature described was the presence of reactive astroglia in spinal cords of fetuses with spina bifida exposed to the amniotic fluid. Astrogliosis has been described before in this model 8 and other spina bifida animal models 20 , 21 , but in our model we detected earlier activation at E15 in the exposed spinal cords from spina bifida fetuses.…”

“…Astrogliosis has been previously described in animal models of spina bifida 18 , 20 at E16.5-E18. Normal astrogenesis in rat fetuses starts at E18 and continues after birth until post-natal day7 26 .…”

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida

“…The establishment and improvement of disease animal models are important for revealing the pathogenesis of human spina bifida, and play key roles in testing novel interventions (Smith et al, 1978;Duru et al, 2001;Danzer et al, 2005). Recent years, researchers have explored the effects of some risk factors by using these animal models (Zhao et al, 2008;Qin et al, 2016), and take further measures such as gene and cell therapy strategies to intervene to reduce the occurrence of perinatal birth defects (Melo-Filho et al, 2009;Turner et al, 2013;Wei et al, 2020a). It is indicated that genetic therapy may become a novel strategy for treating birth defects.…”

State of the art in translating experimental myelomeningocele research to the bedside

“…Weber Guimarães Barreto et al [57] found that there is a high incidence of Chiari malformation in this rat model [57]. The same group (2009) evaluated the effect of steroid therapy on neurological disabilities and reported significant clinical improvement after treatment [58].…”

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