BackgroundThe inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors.MethodsForebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM).ResultsIn midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms.ConclusionsWe documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spect...

the operative risk of stroke and death in the ECST was comparable with other prospective studies and trials in which patients were assessed postoperatively by both a physician and a surgeon. Case fatality and disability after operative stroke are similar to strokes that occur on medical treatment only. Several baseline patient characteristics predict surgical risk and it may be possible to use these characteristics to aid patient selection and surgical audit.

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Thirty-two parasitologically confirmed visceral leishmanisis (VL) patients and 23 healthy, age- and gender-matched controls were recruited between April 2001 and March 2002 and studied for intracellular cytokine production after stimulation in vitro using a Fluorescence Activated Cell Sorter-based intracellular cytokine assay. The VL patients were given i.m. sodium antimony gluconate at a dose of 20 mg/kg bodyweight daily for 28 d and were grouped as responders (n = 11) or non-responders (no response after 28 d of treatment; n = 21). Clinically, the non-responders had longer duration of illness (P < 0.05), larger spleen size (P < 0.05), and higher parasite load (P < 0.05) than responders. The percentage of T helper (Th) cells producing interferon-gamma (IFN-gamma) was significantly higher (P < 0.001) in responders than non-responders. Non-responders had higher IFN-gamma production than control subjects (P < 0.001). The percentage of Th cells producing interleukin-4 (IL-4) was significantly higher in non-responders than responders (P = 0.003) as well as in healthy subjects (P < 0.001). The frequency of IL-4 producing cells in responders and control subjects was similar (P= 0.65). The cytokine polarization index, as calculated by the formula loge IFN-gamma producing cells/loge IL-4 producing cells, was significantly lower in non-responders compared with both responders and control subjects (P = 0.003 and P < 0.001, respectively). The overall cytokine bias in non-responders was skewed towards a IL-4 dominance or Th2-like response and this was primarily due to induction of IL-4.

In older hypertensives, plasma homocysteine levels are associated with increased rates of progressive white matter and hippocampal atrophy.

Background:There is paucity of methodologically sound published studies on intracerebral hemorrhage (ICH) from India, on pub med/embase search.Aims:To explore etiology of ICH and correlate the causes, location, and size of hemorrhage to clinical outcome.Materials and Methods:A hospital-based descriptive study from South Indian eastern coastal town of Puducherry; 60 consecutive subjects aged > 12 years, predominantly of inbred Tamil population, with head CT evidence of intracerebral hemorrhage not associated with trauma and brain tumors, were recruited. Outcome at three months was measured using Glasgow Outcome scale, NIHSS and mortality. SPSS v 19 was used for statistical analysis.Results:Commonest etiological factor was hypertension, followed by bleeding diathesis, thrombolysis for myocardial infarction, and cortical vein thrombosis. Most frequent locations of hematoma were basal ganglia, thalamus, internal capsule, and cerebral and cerebellar parenchyma. Hematoma volume correlated significantly with systolic and mean arterial pressure but not with diastolic blood pressure. Poor outcome was correlated to size (P < 0.05) and intraventricular extension of hematoma (P < 0.05), and to systolic, diastolic and mean arterial pressure, but not to age, gender, smoking, alcoholism, ischemic heart disease, and blood sugar level. Among diabetic patients with ICH, the size of hematoma (P = 0.04) and severity of coma (P = 0.01) at admission were significantly worse compared to the non-diabetic, but not the outcome at three months [Glasgow outcome scale or mortality (P = 0.94 and 0.14)].Conclusions:The location of hemorrhage and correlation with outcome agreed with the patterns described for the non-white races in prior reports. Independence of outcome to diabetic status despite a more severe initial presentation may indicate importance of good care, even in high risk groups.