Mice heterozygous for neurotrophin-3 display enhanced vulnerability to excitotoxicity in the striatum through increased expression of N-methyl-D-aspartate receptors.

The striatum is one of the brain areas most vulnerable to excitotoxicity, a lesion that can be prevented by neurotrophins. In the present study, intrastriatal injection of the N-methyl-d-aspartate receptor (NMDAR) agonist quinolinate (QUIN) was performed in mice heterozygous for neurotrophin-3 (NT3 +/-) or brain-derived neurotrophic factor (BDNF +/-) to analyze the role of endogenous neurotrophins on the regulation of striatal neurons susceptibility to excitotoxic injury. QUIN injection induced a decrease in dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) protein levels that was higher in NT-3 +/- than in BDNF+/- or wild type animals. This enhanced susceptibility was specific for enkephalin- and tachykinin-positive projection neurons, and also for parvalbumin-positive interneurons. However the excitotoxic damage in large interneurons was not modified in NT-3 +/- mice compared with wild type animals. This effect can be related to the regulation of NMDARs by endogenous NT-3. Thus, our results show that there is an age-dependent regulation of NMDAR subunits NR1 and NR2A, but not NR2B, in NT-3 +/- mice. The deficit of endogenous NT-3 induced a decrease in NR1 and NR2A subunits at postnatal day (P) 0 and P3 mice respectively, whereas an upregulation was observed in 12 week old NT-3 +/- mice. This differential effect was also observed after administration of exogenous NT-3. In primary striatal cultures, NT-3 treatment induced an enhancement in NR2A, but not NR2B, protein levels. However, intrastriatal grafting of NT-3 secreting-cells in adult wild type mice produced a down-regulation of NR2A subunit. In conclusion, NT-3 regulates the expression of NMDAR subunits modifying striatal neuronal properties that confers the differential vulnerability to excitotoxicity in projection neurons and interneurons in the striatum.

[Automatic evaluation of total lung capacity and of emphysema involvement with spiral computerized tomography (CT) in obstructive pneumonia]. / Valutazione automatica della capacità polmonare totale e dell'estensione dell'enfisema mediante Tomografia Computerizzata (TC) spirale nella pneumopatia ostruttiva.

OBJECTIVE: To evaluate, in patients with chronic obstructive lung disease or chronic bronchitis, inspiratory helical CT with 3D postprocessing, to measure lung volumes and the amount of emphysema and to compare these measurements with lung function tests. MATERIAL AND METHODS: Seventeen patients with chronic obstructive lung disease disease or chronic bronchitis underwent pulmonary function tests and helical CT after a full inspiration with 3D postprocessing (lower threshold -1024 HU, upper thresholds -200, -300 and -400 HU). Lung inspiratory volumes (TLC-CT) were determined for each model; the amount of emphysema was evaluated by means of an automatic score and a visual score with HRCT. RESULTS: There is a good correlation between automatic and visual scores (p < 0.001); the automatic score had a good correlation with lung function tests, above all with total lung capacity (r = -0.56; p = 0.01) but the visual score had a much closer correlation with DLCO (r = -0.70; p < 0.001). TLC-CT had a significant correlation with pletismographic TLC (TLC-P); the upper threshold -200 HU was more correct (TLC-P = 8011 cc.; TLC-CT 200 = 7138 cc.; r = 0.83; p < 0.001). The volume change of 3D model was about 230 cc. per 100 HU (p < 0.001) modifying upper thresholds, but no change was observed in the volume occupied by emphysema and the percentage of emphysema presented minimal, clinically non significant modifications. DISCUSSION AND CONCLUSIONS: In emphysematous patients, the helical CT with 3D model construction is a good technique to evaluate lung volumes and to quantify emphysema with automatic score; this one, however, probably underscores the extent of pathology; therefore, the addition of a visual score with HRCT is probably worthwhile.