Cerebral Blood Research Articles

Microphysiological Blood-Brain Barrier Systems for Disease Modeling and Drug Development.

The blood-brain barrier (BBB) is a highly controlled microenvironment that regulates the interactions between cerebral blood and brain tissue. Due to its selectivity, many therapeutics targeting various neurological disorders are not able to penetrate into brain tissue. Pre-clinical studies using animals and other in vitro platforms have not shown the ability to fully replicate the human BBB leading to the failure of a majority of therapeutics in clinical trials. However, recent innovations in vitro and ex vivo modeling called organs-on-chips have shown the potential to create more accurate disease models for improved drug development. These microfluidic platforms induce physiological stressors on cultured cells and are able to generate more physiologically accurate BBBs compared to previous in vitro models. In this review, different approaches to create BBBs-on-chips are explored alongside their application in modeling various neurological disorders and potential therapeutic efficacy. Additionally, organs-on-chips use in BBB drug delivery studies is discussed, and advances in linking brain organs-on-chips onto multiorgan platforms to mimic organ crosstalk are reviewed.

Development of a selective estrogen β‐receptor phytoestrogen formulation – PhytoSERM – for the reduction of Alzheimer’s risk and relief of menopausal symptoms in women: a phase 2 randomized clinical trial framework

AbstractBackgroundThe greatest risk factors for Alzheimer’s disease (AD) are age, APOɛ4 allele and female sex. The estimated lifetime risk for AD is 19.5% for women compared to 10.3% in men. Accumulating evidence points to life‐time estrogen exposure as a protective factor against cognitive decline and AD in women, and to the menopause transition as a trigger for an existing AD predisposition. Estrogen replacement therapy (ERT) is effective for sustaining neurological health, but fear of breast cancer is the principal reason menopausal women reject it. Instead, women utilize over the counter products labeled as natural and considered to be safer. Thus, to attain brain protection and address breast protection we developed a rationally designed combination of select ERβ‐selective phytoestrogens that promote brain health to reduce AD risk without increasing breast cell proliferation.MethodA total of 100 participants, 50 per treatment arm, will be enrolled. Eligible participants are woman, 45‐60 years, peri or post‐menopausal (last menstrual period completed ≥ 60 days and ≤ 4 years), MoCA≥22, and experiencing ≥7 hot flashes per day. Participants will be randomized to 50 mg of PhytoSERM or placebo (orally, once‐per‐day) for a 24‐week period. FDG‐PET scans will be conducted at baseline and 24 weeks. Cognitive measures and clinical ratings will be assessed. Hot flashes will be measured both subjectively with a diary and objectively with a digital wristband measuring electrodermal activity.ResultPrimary endpoint is change from baseline to 24 weeks in regional brain glucose metabolism standardized uptake value ratio (SUVR). Secondary outcome measures include cognitive test battery scores, hot flash score and clinical ratings scores. Exploratory measures will include MRI brain volumes, fractional anisotropy, quantitative anisotropy, functional connectivity, and cerebral blood perfusion.ConclusionHerein we present a phase 2 proof‐of‐concept framework to assess the efficacy of PhytoSERM as a potential non‐pharmacologic therapeutic to improve cognitive health and reduce menopausal symptoms. Results from this study will validate previous findings that indicate that PhytoSERM is a safe alternative to hormone therapy and has the potential to sustain neurological health during the menopausal transition.

Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder — study protocol for a randomized clinical trial

BackgroundAnhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.MethodsThis is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow.DiscussionThis study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options.Trial registrationClinicalTrials.gov NCT05347199. April 12, 2022.

Defecation enhances cerebral perfusion and delays fatigue in elite triathletes.

Rectal distension increases regulatory burden to autonomic nervous system in the brain. To determine the effect of rectal defecation on endurance performance and blood supply to the prefrontal brain and sub-navel regions of elite triathletes. Thirteen elite triathletes completed a cycling time trial (80% VO2max) under defecated and non-defecated conditions, using a counterbalanced crossover design. Oxygenation and blood distribution in prefrontal brain and sub-navel regions were monitored by near-infrared spectroscopy (NIRS) during cycling. Defecation moderately decreased systolic blood pressure (-4 mmHg, p < 0.05, d = 0.71), suggesting an alleviation of autonomic nervous activity. During the exercise trials, fatigue (cycling time to exhaustion) occurred when cerebral oxygenation decreased to ~ 5 % below baseline regardless of treatment conditions, suggesting a critical deoxygenation point for sustaining voluntary exertions. Cerebral blood (estimated by total hemoglobin) increased progressively throughout the entire exercise period. Defecation decreased sub-navel oxygenation levels below the non-defecated level, suggesting an increased sub-navel oxygen consumption. Exercise also decreased sub-navel blood distribution, with minimal difference between non-defecated and defecated conditions. Defecation improved blood pooling in the prefrontal brain during exercise (p < 0.05) and enhanced cycling performance in triathletes (Non-defecated: 1624 ± 138 s vs. defecated: 1902 ± 163 s, d = 0.51, p < 0.05). Our results suggest that improved exercise performance after defecation is associated with greater blood availability to compensate deoxygenation in the prefrontal brain region during exercise. Further investigation is needed to examine the role of increasing sub-navel oxygen consumption in the performance improvement after defecation.

Blood-brain barrier-on-a-chip for brain disease modeling and drug testing

The blood-brain barrier (BBB) is an interface between cerebral blood and the brain parenchyma. As a gate keeper, BBB regulates passage of nutrients and exogeneous compounds. Owing to this highly selective barrier, many drugs targeting brain diseases are not likely to pass through the BBB. Thus, a large amount of time and cost have been paid for the development of BBB targeted therapeutics. However, many drugs validated in in vitro models and animal models have failed in clinical trials primarily due to the lack of an appropriate BBB model. Human BBB has a unique cellular architecture. Different physiologies between human and animal BBB hinder the prediction of drug responses. Therefore, a more physiologically relevant alternative BBB model needs to be developed. In this review, we summarize major features of human BBB and current BBB models and describe organ-on-chip models for BBB modeling and their applications in neurological complications.

Endovascular Therapy for Intracranial Giant Cell Arteritis

BackgroundGiant cell arteritis (GCA) is a systemic vasculitis that may cause ischemic stroke. Rarely, GCA can present with aggressive intracranial stenoses, which are refractory to medical therapy. Endovascular treatment (EVT) is a possible rescue strategy to prevent ischemic complications in intracranial GCA but the safety and efficacy of EVT in this setting are not well-described.MethodsA systematic literature review was performed to identify case reports and series with individual patient-level data describing EVT for intracranial GCA. The clinical course, therapeutic considerations, and technique of seven endovascular treatments in a single patient from the authors’ experience are presented.ResultsThe literature review identified 9 reports of 19 treatments, including percutaneous transluminal angioplasty (PTA) with or without stenting, in 14 patients (mean age 69.6 ± 6.3 years). Out of 12 patients 8 (66.7%) with sufficient data had > 1 pre-existing cardiovascular risk factor. All patients had infarction on MRI while on glucocorticoids and 7/14 (50%) progressed despite adjuvant immunosuppressive agents. Treatment was PTA alone in 15/19 (78.9%) cases and PTA + stent in 4/19 (21.1%). Repeat treatments were performed in 4/14 (28.6%) of patients (PTA-only). Non-flow limiting dissection was reported in 2/19 (10.5%) of treatments.The indications, technical details, and results of PTA are discussed in a single illustrative case. We report the novel use of intra-arterial calcium channel blocker infusion (verapamil) as adjuvant to PTA and as monotherapy, resulting in immediate improvement in cerebral blood flow.ConclusionEndovascular treatment, including PTA with or without stenting or calcium channel blocker infusion, may be effective therapies in medically refractory GCA with intracranial stenosis.

Cerebral small vessel disease and blood pressure variability

Annotation. Cerebral small vessel disease (CSVD) contributes up to about 25% of strokes and is the second most common cause of dementia and cognitive decline. Hypertensive arteriolosclerosis is the leading cause of CSVD, hence understanding its relationships with blood pressure changes, including blood pressure variability (BPV), is crucial. The aim of the research was to find out relationships between blood pressure parameters and such MRI-features of CSVD, as white matter hyperintensity (WMH), lacunes, perivascular spaces (PVS), brain atrophy in acute-stroke patients during hospitalization time. 160 participants enrolled in our study (56,3% were male, average age – 61,05±10,95, hospitalization time – 10,46 days). Statistical analysis was performed in the GNU Project software packages (2020). GNU PSPP (Version 1.4.1) [Computer Software]. Free Software Foundation. Boston, MA and The jamovi project (2021). Jamovi (Version 2.0) [Computer Software]. MRI was assessed according to “STRIVE” guidelines for cerebral vessel disease. We measured such BP parameters as mean systolic BP, mean diastolic BP, standard deviation and coefficient of variability for both systolic and diastolic BP. A moderate positive correlation was found between systolic BP variability and WMH severity (r=0.3, p=0.03). There was also a tendency for association between systolic BP variability and enlarged PVS at the basal ganglia level, but it was not significant (p=0.09). There was also a significant relationship between mean systolic BP and WMH severity (r=0.3, p&lt;0.005), mean systolic BP and enlarged PVS at the basal ganglia level (r=0.3, p&lt;0.01), mean systolic BP and total CSVD burden (r=0.3, p&lt;0.005). Systolic BP and its variability are associated with WMH and enlarged PVS, which may provide valuable diagnostic and prognostic data about subtypes of CSVD and the consequences of vascular damage to the brain. Systolic BP variability targeting might be beneficial for prevention of CSVD progression.

A deformation model of pulsating brain tissue for neurosurgery simulation

Background and objectives: For neurological simulation, an accurate deformation model of brain tissue is of key importance for faithful visual feedback. Existing models, however, do not take into account intracranial pulsation, which degrades significantly the realism of visual feedback.Methods: In this paper, a finite element model incorporating intracranial pressure is proposed for simulating brain tissue deformation with pulsation. An implicit Euler method is developed to calculate the deformation of brain tissue. A circuit model of intracranial pressure dynamics is established based on cerebral blood and cerebrospinal fluid circulations. The intracranial pulsation of pressure is introduced into the deformation model, so that the simulated brain tissues pulsate with a rhythm in accord with the changes of intracranial pressure, which resembles real-life neurosurgery.Results and Conclusions: The experimental implementation of the proposed deformation model and the calculation method shows that it provides realistic simulation of brain tissue pulsation and real-time performance is achieved on an ordinary computer for certain procedures of neurosurgery.

Blood-brain barrier crossing using magnetic stimulated nanoparticles

Due to the low permeability and high selectivity of the blood-brain barrier (BBB), existing brain therapeutic technologies are limited by the inefficient BBB crossing of conventional drugs. Magnetic nanoparticles (MNPs) have shown great potential as nano-carriers for efficient BBB crossing under the external static magnetic field (SMF). To quantify the impact of SMF on MNPs' in vivo dynamics towards BBB crossing, we developed a physiologically based pharmacokinetic (PBPK) model for intraperitoneal (IP) injected superparamagnetic iron oxide nanoparticles coated by gold and conjugated with poly (ethylene glycol) (PEG) (SPIO-Au-PEG NPs) in mice. Unlike most reported PBPK models that ignore brain permeability, we first obtained the brain permeabilities with and without SMF by determining the concentration of SPIO-Au-PEG NPs in the cerebral blood and brain tissue. This concentration in the brain was simulated by the advection-diffusion equations and was numerically solved in COMSOL Multiphysics. The results from the PBPK model after incorporating the brain permeability showed a good agreement (regression coefficient R2 = 0.848) with the in vivo results, verifying the capability of using the proposed PBPK model to predict the in vivo biodistribution of SPIO-Au-PEG NPs under the exposure to SMF. Furthermore, the in vivo results revealed that the distribution coefficient from blood to brain under the exposure to SMF (4.01%) is slightly better than the control group (3.68%). In addition, the modification of SPIO-Au-PEG NPs with insulin (SPIO-Au-PEG-insulin) showed an improvement of the brain bioavailability by 24.47% in comparison to the non-insulin group. With the SMF stimulation, the brain bioavailability of SPIO-Au-PEG-insulin was further improved by 3.91% compared to the group without SMF. The PBPK model and in vivo validation in this paper lay a solid foundation for future study on non-invasive targeted drug delivery to the brain.

A prospective cohort study about the effect of repeated living high and working higher on cerebral autoregulation in unacclimatized lowlanders

Cerebral autoregulation (CA) is impaired during acute high-altitude (HA) exposure, however, effects of temporarily living high and working higher on CA require further investigation. In 18 healthy lowlanders (11 women), we hypothesized that the cerebral autoregulation index (ARI) assessed by the percentage change in middle cerebral artery peak blood velocity (Δ%MCAv)/percentage change in mean arterial blood pressure (Δ%MAP) induced by a sit-to-stand maneuver, is (i) reduced on Day1 at 5050 m compared to 520 m, (ii) is improved after 6 days at 5050 m, and (iii) is less impaired during re-exposure to 5050 m after 7 days at 520 m compared to Cycle1. Participants spent 4-8 h/day at 5050 m and slept at 2900 m similar to real-life working shifts. High/low ARI indicate impaired/intact CA, respectively. With the sit-to-stand at 520 m, mean (95% CI) in ΔMAP and ΔMCAv were − 26% (− 41 to − 10) and − 13% (− 19 to − 7), P < 0.001 both comparisons; mean ± SD in ARI was 0.58 ± 2.44Δ%/Δ%, respectively. On Day1 at 5050 m, ARI worsened compared to 520 m (3.29 ± 2.42Δ%/Δ%), P = 0.006 but improved with acclimatization (1.44 ± 2.43Δ%/Δ%, P = 0.039). ARI was less affected during re-exposure to 5050 m (1.22 ± 2.52Δ%/Δ%, P = 0.027 altitude-induced change between sojourns). This study showed that CA (i) is impaired during acute HA exposure, (ii) improves with living high, working higher and (iii) is ameliorated during re-exposure to HA.

Intraoperative neurophysiological monitoring during urgent surgical extracranial internal carotid artery recanalization

ObjectiveThe clinical outcome of surgical extracranial internal carotid artery (eICA) recanalization may be adversely affected by intraoperative ischemia. Median nerve somatosensory evoked potential (SEP) amplitude correlates well with cerebral blood flow.Our study presents the value of intraoperative SEP and selective shunting in the prevention of intraoperative ischemia development during urgent eICA recanalization. MethodsProspective recruitment of patients with acute unilateral eICA occlusion. All underwent surgical recanalization with intraoperative monitoring of scalp median SEPs. Preoperative clinical findings, cerebral collaterals, and 3 month functional outcome were evaluated. ResultsThe cohort consisted of 33 patients. Intraoperative SEP amplitude decreased significantly in 6 (18.2%). An intraluminal shunt was inserted twice (6.1%), surgical complications occurred in 6 (18.2%), intracerebral hemorrhage was not found.Favorable outcome 3 months after surgery according to the modified Rankin scale (mRS 0–2) was achieved in 28 (84.8%), 3 patients died (9.1%). ConclusionsIntraoperative SEP during urgent eICA recanalization seems to be beneficial.Thanks to the effective measure based on the intraoperative SEP changes, the clinical outcome in four(12.1%) could be positively affected. SignificanceThe results suggest that selective shunting based on intraoperative median SEPs may prevent intraoperative ischemia and may improve overall outcome of urgent eICA recanalization.

Effects of acupuncture combined with Brunnstrom staging on upper-limb motor function, cerebral arterial blood flow velocity, and brain function remodeling after stroke

Effects of acupuncture combined with Brunnstrom staging on upper-limb motor function, cerebral arterial blood flow velocity, and brain function remodeling after stroke

Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse

Aging-related cognitive decline is an emerging health crisis; however, no established unifying mechanism has been identified for the cognitive impairments seen in an aging population. A vascular hypothesis of cognitive decline has been proposed but is difficult to test given the requirement of high-fidelity microvascular imaging resolution with a broad and deep brain imaging field of view, which is restricted by the fundamental trade-off of imaging penetration depth and resolution. Super-resolution ultrasound localization microscopy (ULM) offers a potential solution by exploiting circulating microbubbles to achieve a vascular resolution approaching the capillary scale without sacrificing imaging depth. In this report, we apply ULM imaging to a mouse model of aging and quantify differences in cerebral vascularity, blood velocity, and vessel tortuosity across several brain regions. We found significant decreases in blood velocity, and significant increases in vascular tortuosity, across all brain regions in the aged cohort, and significant decreases in blood volume in the cerebral cortex. These data provide the first-ever ULM measurements of subcortical microvascular dynamics in vivo within the context of the aging brain and reveal that aging has a major impact on these measurements.

1,2,4-Triazole Derivative Alleviated Cerebral Edema and Blood Brain Barrier Permeability after Ischemia-Reperfusion Injury by Regulating Mmp9

1,2,4-Triazole Derivative Alleviated Cerebral Edema and Blood Brain Barrier Permeability after Ischemia-Reperfusion Injury by Regulating Mmp9

Хроническая церебральная венозная дисфункция: взгляд на проблему

В статье представлен аналитический обзор результатов отечественных и зарубежных исследований по проблеме хронических нарушений мозгового венозного кровообращения, которым уделяют меньше внимания в сравнении с патологией артериальной системы из-за нечеткости проявлений, особенно ранних, анатомической изменчивости венозного русла даже у здоровых, сложности верификации диагноза и т.д. Когда баланс артериального притока и венозного оттока нарушается и это нарушение прогрессирует, развиваются необратимые изменения в других структурах полости черепа — в первую очередь страдает головной мозг (что согласуется с концепцией Монро — Келли). Хронические нарушения церебрального венозного кровообращения могут иметь разные причины и разную степень выраженности. Синдром хронической церебральной венозной дисфункции, терминологически принятый у нас, в некоторых странах рассматривается как хроническая венозная цереброспинальная недостаточность, что подчеркивает патогенетическую связь нарушений церебрального венозного кровотока с внечерепными венами, что, на наш взгляд, является логичным и обоснованным. Признание хронической цереброспинальной венозной недостаточности вызвало значительный интерес к изучению роли внечерепной венозной патологии и вариантов ее развития. Несмотря на то, что диагноз изначально был основан на допплерографической сонографии, пока не установлено диагностических способов визуализации, неинвазивных или инвазивных, которые могут служить золотым стандартом для выявления венозных отклонений, свидетельствующих о хронической цереброспинальной венозной недостаточности. Обсуждаются результаты ряда исследований, в частности, гипотезы о роли хронической цереброспинальной венозной недостаточности в патогенезе рассеянного склероза и многих сопутствующих клинических проявлений. Анализируется общность по патогенезу идиопатической внутричерепной гипертензии, болезни Меньера, синдрома спондилогенной вертебрально-базилярной недостаточности. Акцентируется внимание и на другом мнении ученых, которые повышение венозного кровенаполнения головного мозга и других образований полости головы при определенных условиях рассматривают как компенсаторную реакцию. Рассматриваются анатомо-физиологические особенности венозной системы черепной полости, обосновывающие клинические проявления венозной дисфункции, способы диагностики и лечения патологии. Обобщая вышесказанное отметим, что хроническое нарушение циркуляции венозной крови в полости черепа в значительной степени связано с проблемами внечерепного венозного кровотока и не только само по себе является достаточно характерным синдромокомплексом, который негативно влияет не только на неврологические функции за счет гипоксии мозга и метаболических изменений, ухудшает качество жизни, но и на течение или имеет патогенетическую связь с другими заболеваниями, в частности, может сопровождаться различным уровнем артериального давления.

Visit-to-Visit Blood PressureVariations and Hemodynamic Deterioration in Atherosclerotic Major Cerebral ArteryDisease

ObjectiveVisit-to-visit variations in blood pressure (BP) in patients with atherosclerotic major cerebral artery disease could impair the function of cerebral collaterals, leading to hemodynamic deterioration at follow-up. However, few studies have investigated the relationship between visit-to-visit BP variability and changes in hemodynamic parameters at follow-up. Materials and methodsWe evaluated 35 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischemic episodes during follow-up (mean: 35 ± 20 months); these patients had a three-time visit for positron emission tomography examinations with 15O-gas. Differences in the mean hemispheric values of hemodynamic parameters in the cortical territory of the diseased artery between the first and third examinations (changes at follow-up) were correlated with the coefficient of variation (CoV) in three systolic BP (SBP) values at the three examinations (BP variability during follow-up). ResultsCoV values were negatively correlated with changes in oxygen metabolism or cerebral blood flow/cerebral blood volume (CBF/CBV) ratio. In 17 patients with higher CoV values (> group median, 0.072), decreases in CBF, cerebral metabolic rate of oxygen, and CBF/CBV ratio were observed at follow-up; CBV decreased in 18 patients without elevated CoV. A higher CoV was associated with a lack of statin use. ConclusionIn patients with atherosclerotic major cerebral artery disease, high visit-to-visit SBP variations during follow-up may be associated with deterioration in cerebral hemodynamics and metabolism.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated.Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0–45th min) and with PEP = 10 cmH2O (PEP10, 46–90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10.Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (−16 ± 14 cm.s–1) and cardiac output (−0.7 ± 1.2 L.min–1) together with a reduced stroke volume (−9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (−1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043).Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

MO537INTERACTION OF PLASMA HOMOCYSTIENE, RENAL FUNCTION AND CARDIO-METABOLIC RISK FACTORS- AN OBSERVATION IN A RURAL POPULATION OF BANGLADESH

Abstract Background and Aims Elevated plasma total homocystiene (tHcy) levels are associated with atherosclerotic diseases in coronary, cerebral and peripheral blood vessels. It is possible that hyperhomocysteinemia may lead to intrarenal arteriosclerotic lesions and decline in GFR or impaired renal function. Aim of this study was to elucidate the association of plasma homocystiene level with renal function and cardiovascular risk factors in rural population. Method A well defined rural area was selected. Study subjects were identified by computer generated random numbers after entering household listings and then Kish table was used to choose a participant. Adult subjects (≥18 years) were only included. The approached participant was explained the purpose, if consented, then given an appointment to be present at a research hospital on a separate date for clinical and biochemical evaluation. A face to face interview was conducted. Clinical history, physical examination anthropometrics were recorded on data sheet. Fasting blood sample and morning spot urine was collected. Then serum tHcy was measured by chemiluminescent microparticle immunoassay (CMIA) technology. Study population were investigated with Spot urine ACR, Fasting glucose, serum lipid profile, creatinine, homocysteinine , Folic acid and Vit B12. Results Early results of 234 random subjects are presented here. The mean age was 41 ± 13(18-92) years with male 33% and female 67%. Mean eGFR was 99± 26 ml/min, tHcy 11.6 ± 5.9 μmol/l, Vit B12 329 ± 187 pg/ml and Folic Acid 5.57 ± 2.63 ng/ml. A tHcy cut-off value in study subjects ≥15 μmol/l was seen in 17 % and &amp;lt;15 μmol/l in 83%. Serum creatinine, Uric Acid, Cholesterol, LDL was significantly higher and Vit B12, Folic acid lower in tHcy ≥15 μmol/l group. Further grouping showed tHcy level was significantly higher in Vit B12&amp;lt;200 pg/ml and Folic acid &amp;lt;3ng/l group. Correlation studies showed homocystiene positively correlated with age, systolic blood pressure, creatinine, LDL and negatively with Folic acid and Vit B12. Conclusion Our findings suggest that elevated plasma homocystiene level might influence and are associated with altered markers of renal, cardiac and metabolic risk factors in rural population. Preventive approaches are required towards this issue as larger population segment belongs to rural areas.

Are acute sitting-induced changes in inflammation and cerebrovascular function related to impaired mood and cognition?

PurposeSedentary behaviour is negatively associated with mood and cognition, yet how acute sitting contributes to these overall associations is unknown. Since sitting heightens inflammation and impairs cerebrovascular function, this study investigated the hypothesis that these sitting-induced changes are related to impaired mood and cognition.MethodsTwenty-five healthy desk workers (18 male, 28.3 ± 7.5 years, BMI: 24.2 ± 3.3 kg∙m−2) were recruited. During laboratory visit one, participants were familiarised with cognitive performance tests measuring executive function, attention and working memory. During laboratory visit two, participants completed 6 h of continuous, uninterrupted sitting. At baseline and after 6 h, serum markers of inflammation, middle cerebral artery blood flow velocity (MCAv), cerebrovascular carbon dioxide reactivity (CVR), dynamic cerebral autoregulation (CA), cognitive performance and mood (positive and negative affect, alert, contented and calm) were assessed. Data were analysed using paired-samples t tests and correlation analyses.ResultsFollowing sitting, C-reactive protein (∆-1.0 µg/ml) and tissue plasminogen activator (∆-360.4 pg/ml) decreased (p < 0.05), MCAv reduced (∆-2.9 cm∙s−1, p = 0.012) and normalised gain increased in the very low frequency range, indicating impaired CA (∆ + 0.22%·mmHg−1, p = 0.016). Positive affect (∆-4.6, p < 0.001), and alert (∆-10.6 p = 0.002) and contented (∆-7.4, p = 0.006) mood states also decreased following sitting. No significant changes in interleukin-6, tumour necrosis factor-alpha, von Willebrand factor, CVR or cognitive performance were observed (p > 0.05). The observed changes in inflammation and cerebrovascular function were not related to changes in mood (p > 0.05).ConclusionAlterations in inflammation or cerebrovascular function following six hours of prolonged, uninterrupted sitting are not related to the observed reductions in mood, indicating other mechanisms underlie the relationship between acute sitting and mood disturbances.

Diagnostic Value of Color Doppler Detection of Perinatal Umbilical Artery and Middle Cerebral Artery Blood Flow in Neonates with Brain Injury

Diagnostic Value of Color Doppler Detection of Perinatal Umbilical Artery and Middle Cerebral Artery Blood Flow in Neonates with Brain Injury