IL-12p40 Deficiency Leads to Uncontrolled Trypanosoma cruzi Dissemination in the Spinal Cord Resulting in Neuronal Death and Motor Dysfunction

Chagas' disease is a protozoosis caused by Trypanosoma cruzi that frequently shows severe chronic clinical complications of the heart or digestive system. Neurological disorders due to T. cruzi infection are also described in children and immunosuppressed hosts. We have previously reported that IL-12p40 knockout (KO) mice infected with the T. cruzi strain Sylvio X10/4 develop spinal cord neurodegenerative disease. Here, we further characterized neuropathology, parasite burden and inflammatory component associated to the fatal neurological disorder occurring in this mouse model. Forelimb paralysis in infected IL-12p40KO mice was associated with 60% (p<0.05) decrease in spinal cord neuronal density, glutamate accumulation (153%, p<0.05) and strong demyelization in lesion areas, mostly in those showing heavy protein nitrosylation, all denoting a neurotoxic degenerative profile. Quantification of T. cruzi 18S rRNA showed that parasite burden was controlled in the spinal cord of WT mice, decreasing from the fifth week after infection, but progressive parasite dissemination was observed in IL-12p40KO cords concurrent with significant accumulation of the astrocytic marker GFAP (317.0%, p<0.01) and 8-fold increase in macrophages/microglia (p<0.01), 36.3% (p<0.01) of which were infected. Similarly, mRNA levels for CD3, TNF-alpha, IFN-gamma, iNOS, IL-10 and arginase I declined in WT spinal cords about the fourth or fifth week after infection, but kept increasing in IL-12p40KO mice. Interestingly, compared to WT tissue, lower mRNA levels for IFN-gamma were observed in the IL-12p40KO spinal cords up to the fourth week of infection. Together the data suggest that impairments of parasite clearance mechanisms in IL-12p40KO mice elicit prolonged spinal cord inflammation that in turn leads to irreversible neurodegenerative lesions.

Weight and neuro-psycho-motor development in children discharged from neonatal intensive care unit

Background: Low birth weight affects child growth and development, requiring the intensive use of health services. There are conversely proportional associations between prematurity and academic performance around the world. In this study we evaluated factors involved in weight and neuropsychomotor profile in one and two years old discharged from Intensive Care Units (ICU). Methods/Design: We investigated 203 children from the ICU who were followed for 24 +/- 4 months. The research was conducted by collecting data from medical records of patients in a Follow-up program. We investigated the following variables: inadequate weight at one year old; inadequate weight at two years old and a severe neurological disorder at two years old. Results: We observed increase of almost 20% in the proportion of children which weighted between the 10th and 90th percentiles and decrease of around 40% of children below the 15th percentile, from one to two years old. In almost 60% of the cases neuropsychomotor development was normal at 2 years old, less than 15% of children presented abnormal development. Variables that remained influential for clinical outcome at 1 and 2 years old were related to birth weight and gestational age, except for hypoglycemia. Neurological examination was the most influential variable for severe neurological disturbance. Conclusion: Hypoglycemia was considered a new fact to explain inadequate weight. The results, new in Brazil and difficult in terms of comparison, could be used to identify risk factors and for a better approach of newborn discharged from ICUs.