Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may escalate their dose because of the development of tolerance. We examined the influence of intermittent adolescent MDMA exposure on the behavioral, physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 5-hydroxytryptamine 1A (5-HT 1A ) receptor challenge. Male Sprague-Dawley rats were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 35 to 60. One week later on PD 67, animals were challenged with either multiple doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT 1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA challenge, completely blocked the locomotor hypoactivity otherwise observed on the day after the challenge, and also prevented MDMA-induced serotonin neurotoxicity assessed on PD 74 by measuring regional [3 H]citalopram binding to the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a partial attenuation of the serotonin syndrome but not the hypothermic response to the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration on regionalcyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5-HT 1A receptors in the brain or spinal cord. These results suggest that chronic, intermittent MDMA exposure during adolescence induces neuroadaptive changes that can protect against the adverse consequences of a subsequent dose escalation. On the other hand, the same exposure pattern appears to produce a partial 5-HT 1A receptor desensitization, which may negatively influence the therapeutic responses of chronic MDMA users treated with serotonergic agents for various affective or anxiety disorders.The entactogen 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) produces several subjective and somatic effects, including increased emotional closeness, elation, sensory pleasure, empathy, temperature dysregulation, jaw clenching, muscle cramping, and nausea (Parrott, 2002;Green et al., 2003). The short-term affective responses quickly subside with regular use, which may contribute to dose escalation and binging in some individuals (Parrott, 2005). Indications of tolerance to MDMA have also been reported in a number of preclinical studies. For example, MDMA self-administration was found to decrease over time in rhesus monkeys, suggesting a reduction in the reinforcing activity of the drug (Fantegrossi et al., 2004). The ability of MDMA to impair schedule-controlled behavior also seems to change with repeated exposure (Li et al., 1989;LeSage et al., 1993). Most strikingly, monkeys were less sensitive to MDMA-induced disruption of cognitive performance 18 months after chronic MDMA treatment (Frederick and Paule, 1997). Likewise, the dose of MDMA necessary to attenuate consummatory behavior increased after daily exposure (Zacny et al., 1990). On the other hand, the physiological and behavioral responses t...

Postpartum cervical dissections are rare occurrences that require prompt diagnosis to prevent long-term neurologic deficits. Individualized management strategies include medical treatment (anticoagulation therapy, antiplatelet therapy, or anticoagulation and antiplatelet therapy) and endovascular recanalization.

Background and Purpose The middle cerebral artery (MCA) bifurcation is a preferred site for aneurysm formation. Wider bifurcations angles have been correlated with increased risk of aneurysm formation. We hypothesized a link between the presence of MCA aneurysms and the angle morphology of the bifurcation. Methods 3D rotational angiography volumes of 146 MCA bifurcations (62 aneurysmal) were evaluated for angle morphology: parent-daughter angles (larger daughter-Φ1, smaller daughter-Φ2), bifurcation angle (Φ1+Φ2), and inclination angle (γ) between the parent vessel axis and the plane determined by daughter vessels axes. Statistics were evaluated using Wilcoxon rank-sum analysis and area under the ROC curve (AUC). Results Aneurysmal bifurcations had wider inclination angle γ (median 57.8° vs. 15.4°; p<0.0001). 75% of aneurysmal MCAs had γ>10°, compared to 25% non-aneurysmal. Φ1, Φ2, but especially Φ1+Φ2 were significantly larger in aneurysmal bifurcations (median 171.3° vs. 98.1°; p<0.0001). 67% of aneurysmal bifurcations had Φ1+Φ2>161°, compared to 0% non-aneurysmal MCAs. An optimal threshold of 140° was established for Φ1+Φ2 (AUC=0.98). 68% of aneurysms originating off the daughter branches. 76% of them originated off the branch with the largest branching angle, specifically if this was the smaller daughter branch. Wider Φ1+Φ2 correlated with aneurysm neck width, but not dome size. Conclusion MCA bifurcations harboring aneurysms have significantly larger branching angles, and more often originate off of the branch with the largest angle. Wider inclination angle is strongly correlated with aneurysm presence, a novel finding. The results point to altered WSS regulation as a possible factor in aneurysm development and progression.

Object. Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (a) and vertebrobasilar junction (VBJ) angles.Methods. The a and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle a was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles.Results. Angle a was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle a correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger a angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, a increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04).Conclusions. The a angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider. (http://thejns.org/doi/abs/10.3171/2014 key WorDS • vessel morphology • basilar bifurcation • vascular disorders • bifurcation aneurysms • vascular age dependencyAbbreviations used in this paper: AUC = area under the curve; BA = basilar artery; CFD = computational fluid dynamics; IA = intracranial aneurysm; MPR = multiplanar reconstruction; MRA = MR angiography; PCA = posterior cerebral artery; ROC = receiver operating characteristic; VBJ = vertebrobasilar junction; WSS = wall shear stress.