Transactions of the Twenty-Sixth Annual Meeting of the Society for Maternal-Fetal MedicinePostnatal inflammatory rat model for cerebral palsy: Too different from humans
Section snippets
Subcutaneous injections
Pregnant Fischer 344 rats were obtained from Harlan Sprague Dawley (Indianapolis, IN) at embryonic day (E)13. The animals were acclimatized for 48 hours and kept in a 12-hour light/12-hour dark regimen with food available at all times. Animals received humane animal care in compliance with the National Institutes of Health guidelines for Care and Use of Experimental Animals. This protocol was approved by NICHD Animal Care and Use Committee. LPS (lipopolysaccharide, Escherichia coli serotype
Animals
On gestational day 21, 23 pups from 3 litters delivered. There were 6 to 9 pups per litter and 14 pups (n = 7 LPS, n = 7 control) were randomly chosen from the 3 litters for this study. On PNDs 2 through 6 of the neonatal testing, animals on completion of the day's assessment received an injection of LPS or saline. None of the animals displayed signs of clinical inflammation or illness before or after each injection. There was no difference in weight between the LPS-treated and saline-treated
Comment
Neonatal exposure to LPS-induced WMD in the brain and accelerated neurodevelopment and motor tasks in adulthood. This model used a chronic exposure to LPS during the timeperiod when the pre-OLs are present in the rat, mimicing a model of chronic infection during human gestation. Although the inflammatory stimulus successfully induced histologic alterations, the long-term result did not result in a motor phenotype. These are similar to findings from a postnatal hypoxic model18 suggesting that in
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Cited by (20)
Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates long-term structural and functional outcomes in a mouse model
2017, Brain, Behavior, and ImmunityCitation Excerpt :Assessment of motor behaviors in our model is measured over the postnatal period to describe functional motor phenotypes and validate our model as a relevant pre-clinical tool. Acquisition of neurosensorimotor reflexes and function over the neonatal period in mice is used to validate developmental deficits in various rodent models (Alles et al., 2010; Altman and Sudarshan, 1975; Balasubramaniam et al., 2006; Poggi et al., 2005; Roberson et al., 2006; Toso et al., 2005). Forelimb grasp acquisition is significantly delayed in all groups except in mouse pups exposed to LIS-alone (Fig. 6A).
Consumption of broccoli sprouts during late gestation and lactation confers protection against developmental delay induced by maternal inflammation
2016, Behavioural Brain ResearchCitation Excerpt :Several investigators administer the endotoxin directly into the pups after they are born, as opposed to the pregnant dam. Whether this is accomplished intra-ventricularly or intra-peritoneally [39], this method reflects a postnatal environment, as opposed to the in-utero antenatal environment [40]. Overall, the selected model better reflects the FIR in utero and can provide an opportunity to investigate mechanisms of injury and the therapeutic intervention of BrSp.
Inflammatory response and oxidative stress in developing rat brain and its consequences on motor behavior following maternal administration of LPS and perinatal anoxia
2013, International Journal of Developmental NeuroscienceCitation Excerpt :There have been several trials on animal models to test the effects of LPS and PA on motor abilities. Although most of these studies reported impairments on motor performance, they were, however, not reminiscent of those observed in human CP and the adult offspring were able to compensate to the damage occurred (Boksa et al., 1995; Poggi et al., 2005; Strata et al., 2004; Toso et al., 2005; Ujházy et al., 2006; Roberson et al., 2006; Rousset et al., 2013). Using an animal model that mimics a chronic maternal inflammation in association to a perinatal model of anoxia which resulted in increased levels of IL-1, TNF-α (pro-inflammatory cytokines), and DCF (a marker for oxidative stress) we have demonstrated a motor phenotype that is relevant to mimic the human CP condition.
Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: Possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes
2013, Brain, Behavior, and ImmunityCitation Excerpt :Unlike previous studies, no alterations were found in motor activity and spatial learning and memory performance with the exception of a more rapid initial training latency in the RAM. Subtle changes were observed in oligodendroglia and myelin specific genes and NFA-cerebroside fraction during the pre-weaning and adolescent period with no evidence of a decrease in myelin basic protein but a slight transient alteration in the complexity of myelinated processes suggesting an effect on the developing OL similar to previous observations in perinatal infection models (Roberson et al., 2006). The majority of earlier studies demonstrating a profound impact of gestational infection on offspring behavior utilized models with elevated maternal inflammatory factors and reported a disruption in a number of neurobehavioral endpoints (Samuelsson et al., 2006; Smith et al., 2007; Ito et al., 2010).
Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development and NIAAA.
Presented at the 26th Annual Meeting of the Society for Maternal Fetal Medicine, January 30-February 4, 2006, Miami, FL.
Reprints not available from the authors.