Impacts of Microgravity Analogs to Spaceflight on Cerebral Autoregulation.

It is well known that exposure to microgravity in astronauts leads to a plethora physiological responses such as headward fluid shift, body unloading, and cardiovascular deconditioning. When astronauts return to Earth, some encounter problems related to orthostatic intolerance. An impaired cerebral autoregulation (CA), which could be compromised by the effects of microgravity, has been proposed as one of the mechanisms responsible for orthostatic intolerance. CA is a homeostatic mechanism that maintains cerebral blood flow for any variations in cerebral perfusion pressure by adapting the vascular tone and cerebral vessel diameter. The ground-based models of microgravity are useful tools for determining the gravitational impact of spaceflight on human body. The head-down tilt bed rest (HDTBR), where the subject remains in supine position at -6 degrees for periods ranging from few days to several weeks is the most commonly used ground-based model of microgravity for cardiovascular deconditioning. head-down bed rest (HDBR) is able to replicate cephalic fluid shift, immobilization, confinement, and inactivity. Dry immersion (DI) model is another approach where the subject remains immersed in thermoneutral water covered with an elastic waterproof fabric separating the subject from the water. Regarding DI, this analog imitates absence of any supporting structure for the body, centralization of body fluids, immobilization and hypokinesia observed during spaceflight. However, little is known about the impact of microgravity on CA. Here, we review the fundamental principles and the different mechanisms involved in CA. We also consider the different approaches in order to assess CA. Finally, we focus on the effects of short- and long-term spaceflight on CA and compare these findings with two specific analogs to microgravity: HDBR and DI

Comparison of frequency and time domain methods of assessment of cerebral autoregulation in traumatic brain injury.

The impulse response (IR)-based autoregulation index (ARI) allows for continuous monitoring of cerebral autoregulation using spontaneous fluctuations of arterial blood pressure (ABP) and cerebral flow velocity (FV). We compared three methods of autoregulation assessment in 288 traumatic brain injury (TBI) patients managed in the Neurocritical Care Unit: (1) IR-based ARI; (2) transfer function (TF) phase, gain, and coherence; and (3) mean flow index (Mx). Autoregulation index was calculated using the TF estimation (Welch method) and classified according to the original Tiecks' model. Mx was calculated as a correlation coefficient between 10-second averages of ABP and FV using a moving 300-second data window. Transfer function phase, gain, and coherence were extracted in the very low frequency (VLF, 0 to 0.05 Hz) and low frequency (LF, 0.05 to 0.15 Hz) bandwidths. We studied the relationship between these parameters and also compared them with patients' Glasgow outcome score. The calculations were performed using both cerebral perfusion pressure (CPP; suffix 'c') as input and ABP (suffix 'a'). The result showed a significant relationship between ARI and Mx when using either ABP (r=-0.38, P<0.001) or CPP (r=-0.404, P<0.001) as input. Transfer function phase and coherence_a were significantly correlated with ARI_a and ARI_c (P<0.05). Only ARI_a, ARI_c, Mx_a, Mx_c, and phase_c were significantly correlated with patients' outcome, with Mx_c showing the strongest association.This is the accepted manuscript. The final version's available from Nature Publishing at http://dx.doi/10.1038/jcbfm.2014.192

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. METHODS: The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving β-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. RESULTS: Forty-eight patients were included. Median age was 58 years old (36-76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS (P=0.007), sedation (P=0.001), World Federation of Neurosurgery score (P=0.001), Glasgow score (P=0.002), Fisher score (P=0.022), and heart rate (P=0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048-1.818; P=0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171-0.706; P=0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. CONCLUSIONS: In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study

Increased blood glucose is related to disturbed cerebrovascular pressure reactivity after traumatic brain injury.

BACKGROUND: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown. METHODS: To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus. RESULTS: Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008). CONCLUSION: Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s12028-014-0042-

Cerebral vasospasm affects arterial critical closing pressure.

The effect of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH) on critical closing pressure (CrCP) has not been fully delineated. Using cerebral impedance methodology, we sought to assess the behavior of CrCP during CVS. As CrCP expresses the sum of intracranial pressure (ICP) and vascular wall tension, we also explored its role in reflecting changes in vascular tone occurring in small vessels distal to spasm. This retrospective analysis was performed using recordings from 52 patients, diagnosed with CVS through transcranial Doppler measurements. Critical closing pressure was calculated noninvasively using arterial blood pressure and blood flow velocity. Outcome was assessed at both discharge and 3 months after ictus with the Glasgow Outcome Scale. The onset of CVS caused significant decreases in CrCP (P=0.025), without any observed significant changes in ICP (P=0.134). Vasospasm induced asymmetry, with CrCP ipsilateral to CVS becoming significantly lower than contralateral (P=0.025). Unfavorable outcomes were associated with a significantly lower CrCP after the onset of CVS (discharge: P=0.014; 3 months after SAH: P=0.020). Critical closing pressure is reduced in the presence of CVS in both temporal and spatial assessments. As ICP remained unchanged during CVS, reduced CrCP most probably reflects a lower wall tension in dilated small vessels distal to spasm.GVV is supported by an A.G. Leventis Foundation Scholarship, and a Charter Studentship from St Edmund’s College, Cambridge. AGK is supported by a Royal College of Surgeons of England Research Fellowship, a National Institute for Health Research (NIHR) Academic Clinical Fellowship, and a Raymond and Beverly Sackler Studentship. JD is supported by a Woolf Fisher Trust scholarship. PJH is supported by an NIHR Research Professorship, the NIHR Cambridge Biomedical Research Centre and has been appointed as the Surgical Specialty Lead for Neurosurgery, Royal College of Surgeons of England Clinical Research Initiative. JDP and MC are supported by the NIHR Cambridge Biomedical Research Centre and JDP by NIHR Senior Investigator Award. The prospective study16 on which this retrospective analysis was based, was supported by the National Institute of Health Research, Biomedical Research Centre (Neuroscience Theme). MC was supported by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final published version is available from Nature Publishing at http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm2014198a.html

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH. Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal. Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50-67). WFNS scale was 2 (1-4) and the modified Fisher scale was 3 (1-3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (R p = -0.42; p < 0.001). Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies

Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen

L'autorégulation dynamique de la circulation cérébrale. Etude physiopathologique dans les situations à risque cérébrovasculaire

L'autorégulation de la circulation cérébrale est un mécanisme homéostatique qui limite les variations du débit sanguin cérébral lorsque la pression artérielle varie. Elle peut être évaluée par le modèle statique ou par le modèle dynamique. Selon le modèle statique, le débit sanguin cérébral reste constant après des variations stabilisées de la pression artérielle entre une limite basse et une limite haute. Le modèle dynamique appréhende la cinétique de l'autorégulation à partir des variations de la pression artérielle et des vitesses circulatoires cérébrales, à court terme, sur des périodes de l'ordre de 2 à 15 secondes. Il est rationnel de supposer que les perturbations de l'autorégulation dynamique peuvent entraîner une augmentation du risque d'accident vasculaire cérébral. Néanmoins, les états pathologiques associés à une altération de l'autorégulation ne sont pas bien identifiés. Nous avons étudié l'autorégulation dynamique cérébrale dans trois maladies associées à une augmentation du risque d'AVC: syndrome d'apnée obstructive du sommeil, diabète de type 1 et athérome carotidien. L'autorégulation dynamique cérébrale a été quantifiée à partir des fluctuations spontanées de la pression artérielle et des vitesses circulatoires cérébrales grâce à un logiciel ad hoc qui permet de corréler les variations de ces deux paramètres dans le domaine temporel. Nous avons trouvé une nette altération de l'autorégulation dynamique cérébrale dans les trois situations pathologiques étudiées. Dans le syndrome d'apnée obstructive du sommeil, l'effet rémanent de l'hypercapnie nocturne est la cause probable de l'altération de l'autorégulation dynamique cérébrale à l'état de veille, car celle-ci est positivement corrélée à l'index d'apnées-hypopnées. Dans le diabète de type 1, l'altération de l'autorégulation dynamique cérébrale est corrélée à la sévérité de la dysautonomie. Dans l'athérome carotidien, l'altération de l'autorégulation dynamique cérébrale est inversement corrélée à la diminution de la sensibilité du baroréflexe artériel. Les résultats que nous avons obtenus dans le diabète de type 1 et dans les sténoses et occlusions athéromateuses de la carotide sont en faveur du possible rôle causal d'une diminution du tonus sympathique dans l'altération de l'autorégulation dynamique cérébrale. Notre recherche montre que l'autorégulation dynamique cérébrale est altérée dans des situations pathologiques diverses qui ont en commun d'être associées à une majoration du risque vasculaire cérébral. Dans les trois états pathologiques étudiés il existe des anomalies associées susceptibles d'expliquer une diminution du tonus artériel cérébral et, par conséquent de l'autorégulation dynamique. Des études complémentaires sont nécessaires pour évaluer l'impact des perturbations de l'autorégulation cérébrale dynamique sur le risque d'accident vasculaire cérébral.Autoregulation of cerebral blood flow is a homeostatic mechanism which limits the variations of cerebral blood flow when the arterial blood pressure (ABP) changes. The so-called static autoregulation refers to stability of cerebral blood flow when ABP is increased or reduced in a steady fashion on prolonged periods of time. The dynamic approach of cerebral autoregulation is based on the analysis of the rapid adaptive response of cerebral arteries to acute changes in ABP to restore cerebral blood flow to baseline. We assessed dynamic cerebral autoregulation (DCA) in three situations associated with an increased risk of cerebral ischemia: obstructive sleep apnea syndrome, Type 1 diabetes with cardiovascular autonomic neuropathy, and stenosis and occlusions of the cervical carotid artery due to atherosclerosis. DCA was assessed from slow changes in mean cerebral blood flow velocity and mean ABP which were analysed over time using a custom-made validated algorithm. We found a significant impairment of DCA in the three pathological situations that we addressed. In obstructive sleep apnea syndrome, DCA impairment was probably caused by the residual impact of hypercapnia because it correlated to the apnea-hypopnea index. In type 1 diabetes, DCA impairment correlated to the severity of cardiovascular autonomic neuropathy. In atherosclerotic stenosis and occlusions of the cervical carotid artery, DCA impairment inversely correlated to baroreflex sensitivity. In type 1 diabetes with cardiovascular autonomic neuropathy and in carotid atherosclerosis, our results suggest that sympathetic activity enhances DCA. Our research shows that the pathological situations and pathways that can alter DCA are numerous. The physiopathological changes associated with these medical situations can explain a reduction in cerebral vasomotor tone which is responsible for DCA impairment. Further studies are needed to assess the impact of DCA impairment on stroke risk

Skeletal and dento-alveolar effects of fixed intermaxillary appliance for class II correction in adolescents: review of literature

La classe II squelettique, très souvent liée à un déficit de croissance mandibulaire, est une des malocclusions les plus fréquemment rencontrées en orthodontie. Nous sommes souvent confrontés à la nécessité de devoir corriger ce décalage à l’adolescence. Un traitement capable de stimuler rapidement la croissance mandibulaire semble donc indiqué chez ces patients. De nos jours, différents appareils fixes intermaxillaires sont à notre disposition, notamment le ForsusTM, système actuellement le plus étudié. La revue de la littérature menée, avait pour objectif de comparer les effets squelettiques et dento-alvéolaires de ces appareils. Elle a été réalisée à partir des bases de données Cochrane, PubMed, Scopus et Google Scholar. Seuls les articles répondant à tous nos critères d’inclusion ont été sélectionnés. La recherche a identifié 15 articles. 12 de ces articles ont mis en évidence un effet mixte de ces appareils avec une dominance dento-alvéolaire, 2 articles concluaient à des effets que dento-alvéolaires et 1 n’étudiait que la position de l’incisive mandibulaire. Les effets de ces appareils sont à ponctuer en fonction de chaque adolescent dont la croissance résiduelle est variable.Skeletal class II, very often related to mandibular growth deficit, is one of the most common malocclusions in orthodontics. We are often faced with the need to correct this gap in adolescence. A treatment capable of rapidly stimulating mandibular growth seems indicated in these patients. Various fixed intermaxillary devices are available, notably the ForsusTM, currently the most studied system. This review of literature aims to compare skeletal and dento-alveolar effects of this aplliances. The search was performed from databases Cochrane, PubMed, Scopus and Google Scholar. Only the articles meeting all of our inclusion criteria were selected. The serach identified 15 articles. 12 of this articles found a mixed effect of these appliances with dento-alveolar dominance, 2 articles concluded to only dento-alveolar effects and 1 studied only the position of mandibular incisior. The effetcs of these appliances are to moderate according to each adolescent whose residual growth is variable