Cerebral Palsy

Streptococcus pneumoniae is the most common bacterial cause of community-acquired meningitis worldwide. Despite optimal antibiotic therapy and supportive care, the mortality of this condition remains very high at 20-30% in the developed world and over 60% in under-resourced hospitals. In developed countries, approximately half of the survivors suffer intellectual impairment, hearing loss, or other neurological damage. There is an urgent need for more information about the mechanisms of brain damage and death in pneumococcal meningitis so that new treatments can be designed. Using proteomic techniques and bioinformatics, the protein content of cerebrospinal fluid can be examined in great detail. Animal models have added greatly to our knowledge of possible mechanisms and shown that hippocampal apoptosis and cortical necrosis are distinct mechanisms of neuronal death. The contribution of these pathways to human disease is unknown. Using proteomic techniques, neuronal death pathways could be described in CSF samples. This information could lead to the design of novel therapies to minimize brain damage and lower mortality. This minireview will summarize the known pathogenesis of meningitis, and current gaps in knowledge, that could be filled by proteomic analysis.

Iodine deficiency is considered to be one of the most common nutrition disorders in the world and the world’s greatest single cause of preventable brain damage. Despite a worldwide application of successful iodine supplementation programs over the last four decades, iodine deficiency remains a major public health problem throughout the world. All European countries except Iceland have experienced this health and socioeconomic threat to a greater or lesser extent. The fact that mild to severe iodine deficiency persists in many European countries may have important public health consequences, including impaired intellectual development of infants and children. Iceland has in the past been known for its high iodine status, based on results from studies of iodine status from 1939, 1988, and 1998 suggested to be due to high fish consumption. Fish together with milk and other dairy products are the main sources of iodine in the Icelandic diet, but iodized salt is not commonly used. In recent years fish and dairy intake has decreased, especially among young people. In this paper, historical data on iodine status and iodine intake in Iceland is reviewed and the need for further studies as well as possible need for public health actions evaluated.

This review addresses recent and not so recent works that emphasize on the mechanisms by which liver damage can induce encephalopathy. Hepatic encephalopathy constitutes an intriguing complication in severe liver acute and chronic disease, whose pathophysiology is still not completely understood. In this pathology, alterations in normal brain function are associated with morphological and functional impairments of astrocytes and neurons. A wide spectrum of psychoneurological symptoms has been described and the anatomical substratum is usually associated with brain edema and intracranial hypertension, as well as with changes in the function of brain cells. An increase in blood ammonia, toxic to the brain, depends on the activity of the enzyme glutamine synthetase, the glutamine/glutamate cycle and the brain capacity to eliminate toxic substances. When the concentration of the excitotoxic neurotransmitter glutamate is increased, it acts as a toxic agent, especially when its specific transporters are altered and its uptake is decreased. Glutamine has also been recently considered a toxic substance when its concentration is high, and consequently contributes to brain edema. Finally, the formation of reactive oxygen species, basically produced by mitochondria, influence with their toxic action on membrane lipids, proteins and DNA. In conclusion we suggest that at least these four elements are involved directly in the mechanism of hepatic encephalopathy.<br />

This review describes the occurrence of hypoglycemia in young children as a common and serious complication that needs to be avoided because of the high risk of brain damage and mortality. Young age, fasting, and severe infectious disease are considered important risk factors. The limited data on the effect of these risk factors on glucose metabolism in children are discussed and compared with data on glucose metabolism in adults. The observations discussed may have implications for further research on glucose kinetics in young children with infectious disease.

The euryhaline fish, Oreochromis mossambicus was exposed to sub-lethal concentration (30mug/L) of profenofos (PF) for 28 days and allowed to recover for 7 days. Responses were evaluated through antioxidant enzyme activities in various tissues of fish. Glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities showed transient increases in gill, viscera and muscle, but decreased in brain. However, catalase (CAT) and glutathione reductase (GR) were inhibited in gill and viscera. Reduced glutathione (GSH) levels were depleted in all the tissues and a significant induction in lipid peroxidation (LPO) was observed. Significant recovery in all the studied parameters was noticed at the end of recuperation period. The enhanced LPO in the present study suggests that reactive oxygen species (ROS)-induced oxidative damage could be one of the main toxic effect of PF. The increased LPO and alterations in the antioxidant defense system can be used as biomarkers in the pesticide-contaminated aquatic streams.

The aim of the present survey was to review scientific articles dealing with the non-visual (auditory and tactile) forms of neglect to determine: (a) whether behavioural patterns similar to those observed in the visual modality can also be observed in the non-visual modalities; (b) whether a different severity of neglect can be found in the visual and in the auditory and tactile modalities; (c) the reasons for the possible differences between the visual and non-visual modalities. Data pointing to a contralesional orienting of attention in the auditory and the tactile modalities in visual neglect patients were separately reviewed. Results showed: (a) that in patients with right brain damage manifestations of neglect for the contralesional side of space can be found not only in the visual but also in the auditory and tactile modalities; (b) that the severity of neglect is greater in the visual than in the non-visual modalities. This asymmetry in the severity of neglect across modalities seems due to the greater role that the automatic capture of attention by irrelevant ipsilesional stimuli seems to play in the visual modality.

Part of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) activate antigen-presenting cells through Toll-like receptors (TLR) to initiate immune responses. However, controversy remains if TLR4 mediates DAMP signaling due to the confounding effects of potential LPS contamination. To test if TLR4 functions as a true receptor for DAMP, we compared TLR4(pos)- and TLR4(neg)-responders in vitro and in vivo after stimulation with whole necrotic cell (NC) lysates. Using CHO reporter cells transfected with anti-TLR4-siRNAs, TLR4 was found to partially mediate NF-kB activation in response to NC lysates. TLR4(neg) DCs exhibited less I-A(b) expression and nitric oxide secretion than TLR4(pos) DCs upon NC stimulation and this defect was well correlated with diminished presentation of H-Y antigen by TLR4(neg) DCs to I-A(b)-restricted CD4(pos) Marilyn T cells in vitro. Similarly, TLR4(neg) DCs showed significantly less expression of I-A(b), CD80, CD86, and CD40 than TLR4(pos) DCs when NC lysates were injected into peritoneal cavity. Finally, delayed type hypersensitivity response to OVA was significantly decreased in TLR4(neg) mice when NCs were used as an adjuvant. Taken together, our data support the idea that part of the endogenous ligands presented by NCs could activate APCs thru TLR4 and contribute to the development of antigen-specific adaptive immunity. Therefore, endogenous DAMP ligands themselves, not contaminated LPS, activate TLR4 signaling leading to activation of professional antigen presenting cells.

BACKGROUND: Methylmalonic acidemia (MMA) is a multifactorial autosomal recessive inborn error of organic acid metabolism, often presenting with neurological symptoms. As neurological disorders are often related to white matter injury, diffusion tensor imaging (DTI) is an excellent tool for assessment of white matter injury and possibly for diagnosing this disorder. METHODS: We retrospectively analyzed DTI images of 12 patients with MMA (7 males, 5 females, age range: 7 – 12 months, mean age: 9.25 +/- 1.70 months) with negative MRI findings. And another 12 age-matched and gender-matched infants were enrolled as control subjects. Fractional anisotropy (FA) of different white matter tracts of the brain was measured in both groups. RESULTS: For patients with negative MRI findings, compared with healthy infants, a statistically significant reduction in DTI FA value of the frontal white matter, temporal white matter, and occipital white matter was observed (P < 0.01). CONCLUSIONS: In addition to conventional T1W and T2W MR Image, Brain DTI presents a useful, sensitive and complementary tool for the assessment of brain damage in patients with MMA.

Chondroitin sulfate (CS), a polysaccharide moiety of proteoglycans, is one of the major components of the extracellular matrix in the central nervous system and is involved in various cellular events in the formation and maintenance of the neural network. In the developing brain, CS in the milieu of neural stem/progenitor cells (NSPCs) is believed to participate in the regulation of their functions such as proliferation and differentiation. NSPCs are expected to act as a potent cell type in cell replacement therapy for neurodegeneration in various neurological diseases. Recently, it has been shown that transplantation of NSPCs combined with removal of extracellular CS from the host nervous tissues gives a satisfactory outcome in some animal models of nervous tissue injuries including neonatal hypoxic-ischemic injury and adult spinal cord injury. The combination of cell transplantation with modification of the extracellular matrix of the host tissue could be a novel strategy for the treatment of incurable neurodegenerative diseases.

Abstract Brain-derived neurotrophic factor (BDNF) is highly expressed in the developing brain. It has anti-apoptotic abilities, and protects the neonatal brain. In experimental settings in adult animals, pre-treatment with nicotine has shown increased BDNF levels, indicating a possible contribution to nicotine’s anti-apoptotic effect. Apoptosis contributes to the development of brain damage in perinatal asphyxia. We examined the effects of nicotine on apoptosis-inducing factor (AIF), caspase-3 and BDNF in the hippocampus of a neonatal piglet model of global hypoxia. Forty-one anesthetized newborn piglets were randomized to one of four groups receiving different infusions after hypoxia (1) nicotine 130 mug/kg/h, 2) 260 mug/kg/h, 3) adrenaline, and 4) saline, all 2.6 mL/kg/h. Four hours after hypoxia they were euthanized. The left hemisphere/hippocampus was examined by histopathology and immunohistochemistry; the right hippocampus was analyzed using real time PCR. There was a significantly higher expression of BDNF mRNA and protein in the animals treated with nicotine 130 mug/kg/h vs. the saline treated group (mRNA P=0.038; protein P=0.009). There were no differences regarding AIF or caspase-3. We conclude that nicotine (130 mug/kg/h), infused over 1 h after global hypoxia in neonatal piglets, increases levels of both BDNF mRNA and protein in the hippocampus. This might imply neuroprotective effects of nicotine in asphyxiated neonates.