In vivo chronic nicotine exposure differentially and reversibly affects upregulation and stoichiometry of α4ß2 nicotinic receptors in cortex and thalamus.

Studies with heterologous expression systems have shown that the α4ß2 nicotinic acetylcholine receptor (nAChR) subtype can exist in two stoichiometries (with two [(α4)2(ß2)3] or three [(α4)3(ß2)2] copies of the α subunit in the receptor pentamer) which have different pharmacological and functional properties and are differently regulated by chronic nicotine treatment. However, the effects of nicotine treatment in vivo on native α4ß2 nAChR stoichiometry are not well known. We investigated in C57BL/6 mice the in vivo effect of 14-day chronic nicotine treatment and subsequent withdrawal, on the subunit expression and ß2/α4 subunit ratio of (3)H-epibatidine labeled α4ß2*-nAChR in total homogenates of cortex and thalamus. We found that in basal conditions the ratio of the ß2/α4 subunit in the cortex and thalamus is different indicating a higher proportion in receptors with (α4)2(ß2)3 subunit stoichiometry in the thalamus. For cortex exposure to chronic nicotine elicited an increase in receptor density measured by (3)H-epibatidine binding, an increase in the α4 and ß2 protein levels, and an increase in ß2/α4 subunit ratio, that indicates an increased proportion of receptors with the (α4)2(ß2)3 stoichiometry. For thalamus we did not find a significant increase in receptor density, α4 and ß2 protein levels, or changes in ß2/α4 subunit ratio. All the changes elicited by chronic nicotine in cortex were transient and returned to basal levels with an average half-life of 2.8 days following nicotine withdrawal. These data suggest that chronic nicotine exposure in vivo favors increased assembly of α4ß2 nAChR containing three ß2 subunits. A greater change in stoichiometry was observed for cortex (which has relatively low basal expression of (α4)2(ß2)3 nAChR) than in thalamus (which has a relatively high basal expression of (α4)2(ß2)3 nAChR).

Different physiological and behavioural effects of e-cigarette vapour and cigarette smoke in mice.

Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of α4ß2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine-precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence.

Primary intradural extramedullary ependymoma: imaging findings and review of the literature. A case report.

We describe a 32-year-old woman who presented with progressive dorsal back pain. Neither sensory nor motor deficit was reported. Magnetic resonance imaging (MRI) of the dorsal spine revealed a primary intradural extramedullary lesion with severe spinal cord compression. No other lesion was found in the central nervous system. During surgery an intradural extramedullary tumor was found without medullary infiltration and a total removal was achieved under microscopic guidance. The histological diagnosis revealed a benign extramedullary ependymoma. The patient recovery completely after surgery and at a follow-up of 24 months MRI showed no evidence of tumor recurrence. Ependymoma should be taken in account in the differential diagnosis on intradural extramedullary tumours.

Role of magnetic resonance tractography in the preoperative planning and intraoperative assessment of patients with intra-axial brain tumours.

PURPOSE: This study was conducted to assess the possibility of identifying precise white matter tracts situated in proximity to intracranial tumours, to define the anatomical and topographical relations between the same white matter tracts and the tumour, to verify the possibility of integrating tractographic images in the context of a package of three-dimensional anatomical images to send to the neuronavigation system, to assess the impact of this information on surgical planning, and to analyse, both pre-and postoperatively, the patient's clinical conditions as an index of the functional integrity of the fibres themselves. MATERIALS AND METHODS: Twenty-five patients underwent diffusion tensor study prior to neurosurgery. With the use of dedicated software, relative colour maps were obtained and the trajectories of the white matter tracts adjacent to the tumour were reconstructed in three dimensions. These were then processed for preoperative planning. Planning, which was performed with the neuronavigator, was based on analysis of the location of the course of the main white matter tracts adjacent to the lesion (pyramidal tract, optic radiation and arcuate fasciculus). Two neurosurgeons were asked whether the tractography images had modified the access and/or intraoperative approach to the tumour. All patients were clinically assessed both pre-and postoperatively 1 month after the procedure to define the presence of symptoms related to the involvement of the white matter tracts studied and therefore to assess the integrity of the fibres after the operation. RESULTS: In one patient, the tumour was situated away from all the tracts studied and did not compress them in any way. Overall, 40/75 tracts studied had no anatomical relation with the tumour, were not displaced by the tumour or could not be visualised in their entire course. Analysis of the remaining 35 white matter tracts led to an a priori change in the surgical approach for corticotomy in four patients (16%), with no disagreement between the two neurosurgeons and an impact on the extent of resection during surgery in 17 (68%), thus an overall impact on the surgical procedure in 80% of cases. Eight patients showed no symptoms related to the involvement of the white matter tracts studied. In the remaining 17 patients, the symptoms were related to involvement of the pyramidal tract, arcuate fasciculus or optic radiation. At 1-month follow-up, one previously asymptomatic patient reported a speech disorder (transcortical sensory dysphasia); in the remaining 24, symptoms remained unchanged, with a tendency to improvement in 14/17 with symptoms related to involvement of white matter tracts studied. CONCLUSIONS: Magnetic resonance (MR) tractography offers the neurosurgeon an anatomical panoramic view that can improve surgical planning for the resection of intracranial tumours. Despite the high incidence of cases in which the lesion is responsible for changes that hinder the reconstruction of white matter tracts, the technique can change the surgical approach for corticotomy, defines the extent of resection and leads to some change in the procedure in 80% of cases. The improvement of pre-existing symptoms and the absence of new symptoms in the postoperative phase, in our opinion, confirms the value of the technique.

[Non-invasive assessment of epiaortic vessels. Comparison of magnetic resonance angiography with gadolinium, spiral computerized tomography angiography, and digital angiography]. / Valutazione non invasiva dei vasi epiaortici. Confronto tra angiografia con Risonanza Magnetica con gadolinio, angiografia con tomografia Computerizzata spirale e angiografia digitale.

PURPOSE: The aim of the study was to compare gadolinium-enhanced MRA (Gd-MRA), Computed Tomography angiography (CTA) and digital subtraction angiography (DSA) in the evaluation of carotid stenosis. MATERIAL AND METHODS: Thirty patients with US-proven internal carotid artery stenosis over 50%, underwent Gd-MRA, CTA and DSA. Gd-MRA was acquired using the keyhole technique. RESULTS: The overall agreement was 90% for Gd-MRA and 93% for CTA. Gd-MRA and CTA overestimated 5 and 4 cases of mild stenosis and 1 case each of moderate stenosis, respectively. Gd-MRA better delineated ulcerated plaques, tandem lesions and pseudo-occlusions. DISCUSSION AND CONCLUSIONS: Because of the high speed acquisition breath-hold is no longer necessary for Gd-MRA and more delayed phases were analysed when necessary. The main limitation of Gd-MRA was represented by insufficient volume coverage that allowed the visualisation of supraaortic vessels from the arch only in 57% of the cases. Calcified plaques were very well detected by CTA and not by Gd-MRA. In our experience Gd-MRA represents the second step non invasive tool in patients with US-proven carotid stenosis. This leads to avoid conventional angiography in most cases.

Contrast-enhanced color Doppler US in malignant portal vein thrombosis.

PURPOSE: To assess the role of contrast-enhanced color Doppler US in the differential diagnosis of benign and malignant portal vein thrombosis. MATERIAL AND METHODS: Fifty-six patients with portal vein thrombosis underwent color and power Doppler US examination before and after i.v. injection of galactose-palmitic acid suspension. The criterion for diagnosing the presence and extension of thrombosis was the lack of visualization of portal vein flow in a segment of the portal vein. The criterion for diagnosing malignant portal vein thrombosis was the detection of pulsatile arterial flow, either hepatopetal or hepatofugal, in the thrombus. The US data were correlated with the types of portal vein thrombosis. RESULTS: Among the 56 patients, there were 40 benign and 16 malignant portal thromboses. Unenhanced Doppler US detected continuous blood flow in 24 benign thromboses and pulsatile in 3 malignant thromboses. No flow, either continuous or pulsatile, was detected in 16 cases with benign thrombosis and in 13 cases with malignant thrombosis. Contrast-enhanced Doppler US allowed to assess pulsatile flow in 15 cases with malignant thrombosis (94%). The use of pulsatile flow as diagnostic criterion of malignant thrombosis yielded a sensitivity of 57% and a specificity of 95% with conventional Doppler US, whereas contrast-enhanced US achieved a sensitivity of 94% and a specificity of 100%. CONCLUSION: Contrast-enhanced Doppler US is a reliable diagnostic tool for assessing malignant portal vein thrombosis.