Moždana vazomotorna reaktivnost i okluzivna bolest karotidnih arterija

Cerebral autoregulation is a mechanism that enables relatively constant cerebral blood flow during variations of cerebral perfusion pressure. The differences between cerebral blood flow at rest and after administration of a potent vasodilatory stimulus test such as hypercapnia reflect cerebral vasomotor reactivity defined as the vasodilation capacity of cerebral arterioles to external stimuli, providing important information about the cerebral hemodynamic status. Cerebral vasomotor reactivity provides important information about the cerebral hemodynamic status. In this article, cerebral vasomotor reactivity assessment tests are presented, with emphasis on transcranial Doppler, as well as the use of transcranial Doppler in assessing cerebral vasomotor reactivity in carotid stenosis, occlusion, and the importance of cerebral vasomotor reactivity for carotid surgery.Moždana autoregulacija je mehanizam koji omogućava relativno ustaljeni moždani protok krvi za vrijeme promjena tlaka prokrvljenosti mozga. Razlike između moždanog protoka krvi u mirovanju i nakon testa snažne vazodilatacijske stimulacije poput hiperkapnije odražavaju moždanu vazomotornu reaktivnost definiranu kao vazodilatacijski kapacitet moždanih arteriola za vanjske poticaje, pružajući važne podatke o moždanom hemodinamskom statusu. Moždana vazomotorna reaktivnost daje važne informacije o statusu moždane hemodinamike. U članku se prikazuju testovi za procjenu moždane vazomotorne reaktivnosti s naglaskom na transkranijski Doppler, te primjena transkranijskog Dopplera u procjeni moždane vazomotorne reaktivnosti kod karotidne stenoze, okluzije, kao i važnost moždane vazomotorne reaktivnosti za kirurgiju karotidnih arterija

Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair

Variance in brain volume with advancing age: implications for defining the limits of normality

Background: Statistical models of normal ageing brain tissue volumes may support earlier diagnosis of increasingly common, yet still fatal, neurodegenerative diseases. For example, the statistically defined distribution of normal ageing brain tissue volumes may be used as a reference to assess patient volumes. To date, such models were often derived from mean values which were assumed to represent the distributions and boundaries, i.e. percentile ranks, of brain tissue volume. Since it was previously unknown, the objective of the present study was to determine if this assumption was robust, i.e. whether regression models derived from mean values accurately represented the distributions and boundaries of brain tissue volume at older ages. Materials and Methods: We acquired T1-w magnetic resonance (MR) brain images of 227 normal and 219 Alzheimer’s disease (AD) subjects (aged 55-89 years) from publicly available databanks. Using nonlinear regression within both samples, we compared mean and percentile rank estimates of whole brain tissue volume by age. Results: In both the normal and AD sample, mean regression estimates of brain tissue volume often did not accurately represent percentile rank estimates (errors=-74% to 75%). In the normal sample, mean estimates generally underestimated differences in brain volume at percentile ranks below the mean. Conversely, in the AD sample, mean estimates generally underestimated differences in brain volume at percentile ranks above the mean. Differences between ages at the 5th percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects. Conclusions: While more data are required to make true population inferences, our results indicate that mean regression estimates may not accurately represent the distributions of ageing brain tissue volumes. This suggests that percentile rank estimates will be required to robustly define the limits of brain tissue volume in normal ageing and neurodegenerative disease

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Cerebral vasomotor reactivity in Parkinson’s disease, multiple system atrophy and pure autonomic failure

Abstract Parkinson's disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF) are neurodegenerative disorders frequently associated with orthostatic hypotension and syncope, though with different underlying mechanisms. Cerebral hemodynamic responses in these three neurodegenerative diseases are still incompletely studied and it is possible that they would be differentially affected. We measured blood flow velocity (BFV) in the middle cerebral artery (MCA) and vertebral artery (VA) in patients with these disorders and investigated whether cerebral vasomotor reactivity (VMR) differs in these three disorders. Twenty-four patients (9 with PD, 10 with MSA and 5 with PAF) were studied. VMR was assessed in the MCA and VA, using transcranial Doppler (TCD) and Diamox test (injection of 1 g acetazolamide i.v.) with the patients in a recumbent position. The percent difference between BFV before and after acetazolamide injection was defined as VMR% and the results were compared by ANOVA. The mean MCA and VA blood flow velocities were similar in the three disorders and within normal limits for our laboratory. The mean MCA VMR values were 37.5 T 24.0%, 27.9 T 28.0% and 38.0 T 33.9% in PD, MSA and PAF, respectively. The VA VMR values were 22.9 T 23.6%, 32.4 T 38.0% and 18.9 T 18.3%, respectively, with no significant differences between the groups. We conclude that BFV is normal in PD, MSA and PAF and that the VMR, as investigated by TCD and the Diamox test, did not disclose differences in cerebral vasomotor responses between these conditions. D 2005 Published by Elsevier B.V