Internal carotid artery fibromuscular dysplasia in arterial hypertension: Management in clinical practice

Fibromuscular dysplasia (FMD) reminds of a rare form of secondary arterial hypertension occurring in young people and involving the renal arteries. FMD may also involve vertebral, subclavian, mesenteric, iliac arteries and carotid arteries. FMD of internal carotid arteries is a rare finding that is frequently incidental and asymptomatic. It usually occurs in middle-aged women and is secondary to media-intima fibrodysplasia. The carotid artery may be elongated or kinked and associated cerebral aneurysms have been reported. Symptoms including transient ischaemic attack or stroke are uncommon and are related to decrease of blood flow or embolization by platelet aggregates. At the onset, differential diagnosis with vasculitis must be placed. Computed tomography or magnetic resonance imaging (MRI) angiography demonstrates bilateral high-grade stenosis with the characteristic "string of beads" pattern. Antiplatelet medication is the accepted therapy for asymptomatic lesions. Graduated endoluminal surgical dilation is an outmoded therapy, no longer used in most medical centres. Current percutaneous angioplasty is the preferred treatment for symptomatic carotid FMD, but no randomized controlled trials comparing this methodology with surgery is available. The management of a case of arterial systemic FMD in a 52-year-old women, diagnosed after a hypertensive crysis, is discussed. Imaging methods disclosed stenoses of carotid arteries, of celiac tripod and of superior mesenteric artery. Because of high risk associated to endovascular surgery, medical therapy was started. In the first year of follow-up, no events have been reported

Antihypertensive Treatment in the Elderly and Very Elderly: Always “the Lower, the Better?”

Arterial hypertension (HT) is age dependent and, with the prolongation of life expectancy, affects more and more elderly people. In the elderly, HT is a risk factor for organ damage and cardiovascular (CV) events. Both pharmacologic and nonpharmacologic reduction of blood pressure (BP) is associated with a corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical trials have shown that BP lowering is associated with a decrease in stroke and other CV events. Therefore, BP reduction per se appears more important than a particular class of antihypertensive drugs. The benefit of antihypertensive treatment has been confirmed up to the age of 80 years, remaining unclear in the octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is well established, while that of lowering systolic BP below 140 mmHg requires further confirmations

On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System gave the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the GPCR field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion channel, Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor complexes. The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the diversity of receptor function including recognition, trafficking and signalling. We have proposed the molecular phenomenon of receptor-receptor interactions as a good way to understand of how brain function can increase through molecular integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with the corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead to various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting protomer-protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor complexes in discrete brain regions may become an important field for developing novel drugs, including heterobivalent drugs and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via allosteric receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular medicine, leading to novel strategies for drug discovery and treatment of diseases

A feature-based neurocomputational model of semantic memory

According with a featural organization of semantic memory, this work is aimed at investigating, through an attractor network, the role of different kinds of features in the representation of concepts, both in normal and neurodegenerative conditions. We implemented new synaptic learning rules in order to take into account the role of partially shared features and of distinctive features with different saliency. The model includes semantic and lexical layers, coding, respectively for object features and word-forms. Connections among nodes are strongly asymmetrical. To account for the feature saliency, asymmetrical synapses were created using Hebbian rules of potentiation and depotentiation, setting different pre-synaptic and post-synaptic thresholds. A variable post-synaptic threshold, which automatically changed to reflect the feature frequency in different concepts (i.e., how many concepts share a feature), was used to account for partially shared features. The trained network solved naming tasks and word recognition tasks very well, exploiting the different role of salient versus marginal features in concept identification. In the case of damage, superordinate concepts were preserved better than the subordinate ones. Interestingly, the degradation of salient features, but not of marginal ones, prevented object identification. The model suggests that Hebbian rules, with adjustable post-synaptic thresholds, can provide a reliable semantic representation of objects exploiting the statistics of input features

Synaptogenesis in adult-generated hippocampal granule cells is affected by behavioral experiences.

Adult-generated hippocampal immature neurons play a functional role after integration in functional circuits. Previously, we found that hippocampus-dependent learning in Morris water maze affects survival of immature neurons, even before they are synaptically contacted. Beside learning, this task heavily engages animals in physical activity in form of swimming; physical activity enhances hippocampal neurogenesis. In this article, the effects of training in Morris water maze apparatus on the synapse formation onto new neurons in hippocampus dentate gyrus and on neuronal maturation were investigated in adult rats. Newborn cells were identified using retroviral GFP-expressing virus infusion. In the first week after virus infusion, rats were trained in Morris water maze apparatus in three different conditions (spatial learning, cue test, and swimming). Properties of immature neurons and their synaptic response to perforant pathway stimulation were electrophysiologically investigated early during neuronal maturation. In controls, newborn cells showing GABAergic and glutamatergic responses were found for the first time at 8 and 10 days after mitosis, respectively; no cell with glutamatergic response only was found. Twelve days after virus infusion almost all GFP-positive cells showed both synaptic responses. The main result we found was the anticipated appearance of GABAergic synapses at 6 days in learner, cued and swimmer rats, supported also by immunohistochemical result. Swimmer rats showed the highest percentage of GFP-positive neurons with glutamatergic response at 10 and 12 days postmitosis. Moreover, primary dendrites were more numerous at 7 days in learner, cued and swimmer rats and swimmer rats showed the greatest dendritic tree complexity at 10 days. Finally, voltage-dependent Ca(2+) current was found in a larger number of newborn neurons at 7 days postinfusion in learner, cued and swimmer rats. In conclusion, experiences involving physical activity contextualized in an exploring behavior affect synaptogenesis in adult-generated cells and their early stages of maturation

MATERNAL DIETARY LOADS OF ALPHA-TOCOPHEROL DIFFERENTIALLY INFLUENCE FEAR CONDITIONING AND SPATIAL LEARNING IN ADULT OFFSPRING

α-Tocopherol, the main component of vitamin E, is well known to be a radical scavenger, so an increased intake of vitamin E is recommended in complicated pregnancy, to prevent possible fetus damage by free radical. In a previous work, we found that maternal α-tocopherol supplementation affects PKC-mediated cellular signaling and hippocampal synaptic plasticity in developing brain; the latter effect persists in adulthood. Here, adult rats maternally exposed to supranutritional doses of α-tocopherol were evaluated for Contextual Fear Conditioning and spatial learning in Morris Water Maze, two different hippocampus-dependent learning tasks. Moreover, anxiety, spontaneous activity, and explorative drive were also evaluated as factors potentially affecting learning performance. Treated rats showed a different behavior with respect to controls: performance in Contextual Fear Conditioning was improved, while spatial learning tested in Morris Water Maze, was impaired. The improvement of fear response was not ascribable to differences in anxiety level and/or spontaneous activity; thus it appears to be a specific effect of α-tocopherol overloading during brain development. On the contrary, the impaired performance in Morris Water Maze exhibited by treated rats can be in part explained by their enhanced explorative drive. Although extrapolation from rats to humans is difficult, a caveat in assuming supranutritional doses of vitamin E in pregnancy arises from this study

Bdnf expression in rat skeletal muscle after acute or repeated exercise.

Brain derived growth factor (BDNF) gene of rat has a complex structure: at least four 5' untranslated exons regulated by different promoters and one 3' exon containing the encoding region. BDNF is expressed by skeletal muscles in an activity-dependent manner. In this study, BDNF mRNA was analysed by RT-PCR in the soleus muscle following a single (acute) session of running or a training of five days of running (repetitive exercise). Moreover, the expression of the exons was quantitatively analysed by real time RT-PCR. Finally, muscle BDNF protein level was evaluated by western blotting. BDNF mRNA was found to increase over the second day after acute exercise; on the other hand, two peaks (2 and 24 hours after the last session, respectively) in BDNF mRNA level were found after repetitive exercise, but it was similar to that of controls 6 hours after the last session. BDNF protein level progressively increased also after the mRNA went back to the basal level, so suggesting that it cumulates within the cell after acute exercise, whereas it followed the mRNA level time course after repetitive exercise. These results point to the following conclusions: BDNF mRNA is up-regulated by activity, but this response is delayed to the second day after acute exercise; repetitive exercise transiently depresses the expression of BDNF mRNA, so that the over-expression due to the previous day's exercise completely disappears 6 hours after the last exercise session

The impact of different exercise protocols on rat soleus muscle reinnervation and recovery following peripheral nerve lesion and regeneration.

Background: Incomplete functional recovery following traumatic peripheral nerve injury is common, mainly because not all axons successfully regenerate and reinnervate target muscles. Exercise can improve functional outcomes increasing the terminal sprouting during the muscle reinnervation. However, exercise is not a panacea per se. Indeed, the type of exercise adopted dramatically impacts the outcomes of rehabilitation therapy. To gain insight into the therapeutic effects of different exercise regimens on reinnervation following traumatic nerve lesion, we evaluated the impact of different clinically transferable exercise protocols (EPs) on metabolic and functional muscle recovery following nerve crush. Methods: The reinnervation of soleus muscle in adult nerve-crushed rats was studied following 6 days of different patterns (continuous or intermittent) and intensities (slow, mid, and fast) of treadmill running EPs. The effects of EPs on muscle fiber multiple innervation, contractile properties, metabolic adaptations, atrophy, and autophagy were assessed using functional and biochemical approaches. Results: Results showed that an intermittent mid-intensity treadmill EP improves soleus muscle reinnervation, whereas a slow continuous running EP worsens the functional outcome. However, the mid-intensity intermittent EP neither enhanced the critical mediators of exercise-induced metabolic adaptations, namely, PGC-1α, nor improved muscle atrophy. Conversely, the autophagy-related marker LC3 increased exclusively in the mid-intensity intermittent EP group. Conclusion: Our results demonstrated that an EP characterized by a mid-intensity intermittent activity enhances the functional muscle recovery upon a nerve crush, thus representing a promising clinically transferable exercise paradigm to improve recovery in humans following peripheral nerve injuries