Cerebral Alterations Research Articles

Cerebral oxygenation and bioelectrical activity in preterm infants during surfactant replacement therapy with porcine and bovine preparations.

IntroductionSurfactant replacement therapy (SRT) might cause acute changes in cerebral oxygenation and alteration of brain bioelectrical activity. Varying physiologic responses and clinical outcomes were observed when different surfactant preparations were instilled to treat neonatal respiratory distress syndrome (RDS).Material and methodsNeonates born at 26–30 weeks of gestation with RDS requiring intubation and mechanical ventilation were randomized to SRT either with poractant alfa (A) or beractant (B). Saturation (SpO2), heart rate (HR), cerebral tissue oxygenation (StO2) and amplitude-integrated electroencephalography (aEEG) were simultaneously recorded prior to and up to 4 h after SRT.ResultsMean SpO2, HR and StO2 values were comparable between groups at baseline and after SRT. There were differences in mean aEEG voltage before SRT, but amplitudes were within a range considered as normal in both groups. Immediately after SRT and at a few single post-intervention time points mean aEEG voltage was higher in the beractant group. There was a significant difference in the percentage of time with the aEEG signal < 5 μV after SRT between groups (mean 25.7% (A) vs. 16.5% (B), p < 0.05). Quantity of bursts per minute and mean length of inter-burst intervals (IBI) in the aEEG recording varied insignificantly but there was a significant difference in the percentage of IBI > 30 s between groups (52.5% (A) vs. 36.6% (B), p <0.05).ConclusionsThis is the first study assessing brain bioelectrical function and oxygenation while using two different surfactant preparations in a neonate. Cerebral effects of SRT are observed regardless of the type of surfactant, but their magnitude may depend on the preparation and/or dosing used.

Assessment of Cerebral and Cerebellar White Matter Microstructure in Spinocerebellar Ataxias 1, 2, 3, and 6 Using Diffusion MRI.

Development of imaging biomarkers for rare neurodegenerative diseases such as spinocerebellar ataxia (SCA) is important to non-invasively track progression of disease pathology and monitor response to interventions. Diffusion MRI (dMRI) has been shown to identify cross-sectional degeneration of white matter (WM) microstructure and connectivity between healthy controls and patients with SCAs, using various analysis methods. In this paper, we present dMRI data in SCAs type 1, 2, 3, and 6 and matched controls, including longitudinal acquisitions at 12–24-month intervals in a subset of the cohort, with up to 5 visits. The SCA1 cohort also contained 3 premanifest patients at baseline, with 2 showing ataxia symptoms at the time of the follow-up scans. We focused on two aspects: first, multimodal evaluation of the dMRI data in a cross-sectional approach, and second, longitudinal trends in dMRI data in SCAs. Three different pipelines were used to perform cross-sectional analyses in WM: region of interest (ROI), tract-based spatial statistics (TBSS), and fixel-based analysis (FBA). We further analyzed longitudinal changes in dMRI metrics throughout the brain using ROI-based analysis. Both ROI and TBSS analyses identified higher mean (MD), axial (AD), and radial (RD) diffusivity and lower fractional anisotropy (FA) in the cerebellum for all SCAs compared to controls, as well as some cerebral alterations in SCA1, 2, and 3. FBA showed lower fiber density (FD) and fiber crossing (FC) regions similar to those identified by ROI and TBSS analyses. FBA also highlighted corticospinal tract (CST) abnormalities, which was not detected by the other two pipelines. Longitudinal ROI-based analysis showed significant increase in AD in the middle cerebellar peduncle (MCP) for patients with SCA1, suggesting that the MCP may be a good candidate region to monitor disease progression. The patient who remained symptom-free throughout the study displayed no microstructural abnormalities. On the other hand, the two patients who were at the premanifest stage at baseline, and showed ataxia symptoms in their follow-up visits, displayed AD values in the MCP that were already in the range of symptomatic patients with SCA1 at their baseline visit, demonstrating that microstructural abnormalities are detectable prior to the onset of ataxia.

Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density.

Jegou et al. (2012) have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to search for additional proteins whose placental and fetal cortical expression is altered by PAE, along with a subsequent examination of fetal cerebral cortical alterations associated with altered protein expression. Long-Evans rat dams voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Daily ethanol consumption, which resulted in a mean peak maternal serum ethanol concentration of 60.8 mg/dL, did not affect maternal weight gain, litter size, or placental or fetal body weight. On gestational day 20, rat placental: fetal units were removed by Caesarian section. Placental protein expression, analyzed by 2D-PAGE – tandem mass spectroscopy, identified a total of 1,117 protein spots, 20 of which were significantly altered by PAE. To date, 14 of these PAE-altered proteins have been identified. Western blotting confirmed the alterations of two of these placental proteins, namely, annexin-A4 (ANX-A4) and cerebral cavernous malformation protein 3 (CCM-3). Specifically, PAE elevated ANX-A4 and decreased CCM-3 in placenta. Subsequently, these two proteins were measured in fetal cerebral cortex, along with radiohistochemical studies of VEGF binding and histofluorescence studies of microvascular density in fetal cerebral cortex. PAE elevated ANX-A4 and decreased CCM-3 in fetal cerebral cortex, in a pattern similar to the alterations observed in placenta. Further, both VEGF receptor binding and microvascular density and orientation, measures that are sensitive to reduced CCM-3 expression in developing brain, were significantly reduced in the ventricular zone of fetal cerebral cortex. These results suggest that the expression angiogenesis-related proteins in placenta might serve as a biomarker of ethanol-induced alterations in microvascular development in fetal brain.

Looking for a Treatment for the Early Stage of Alzheimer's Disease: Preclinical Evidence with Co-Ultramicronized Palmitoylethanolamide and Luteolin.

Background: At the earliest stage of Alzheimer’s disease (AD), although patients are still asymptomatic, cerebral alterations have already been triggered. In addition to beta amyloid (Aβ) accumulation, both glial alterations and neuroinflammation have been documented at this stage. Starting treatment at this prodromal AD stage could be a valuable therapeutic strategy. AD requires long-term care; therefore, only compounds with a high safety profile can be used, such as the new formulation containing palmitoylethanolamide and luteolin (co-ultra PEALut) already approved for human use. Therefore, we investigated it in an in vivo pharmacological study that focused on the prodromal stage of AD. Methods: We tested the anti-inflammatory and neuroprotective effects of co-ultra PEALut (5 mg/Kg) administered for 14 days in rats that received once, 5 µg Aβ(1–42) into the hippocampus. Results: Glial activation and elevated levels of proinflammatory mediators were observed in Aβ-infused rats. Early administration of co-ultra PEALut prevented the Aβ-induced astrogliosis and microgliosis, the upregulation in gene expression of pro-inflammatory cytokines and enzymes, as well as the reduction of mRNA levels BDNF and GDNF. Our findings also highlight an important neuroprotective effect of co-ultra PEALut treatment, which promoted neuronal survival. Conclusions: Our results reveal the presence of cellular and molecular modifications in the prodromal stage of AD. Moreover, the data presented here demonstrate the ability of co-ultra PEALut to normalize such Aβ-induced alterations, suggesting it as a valuable therapeutic strategy.

Environmental enrichment enhances post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional somatosensory cortex

Environmental enrichment has been reported to promote functional recovery in an ischemic stroke. However, the underlying mechanism remains unclear. This study aimed to investigate the effect of environmental enrichment treatment on post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional primary somatosensory cortex of rats. With laser speckle imaging, we were able to monitor the resting cerebral blood flow alteration in the middle cerebral artery occlusion model. Both 3- and 28-day post-ischemic infarct volumes were then examined with triphenyltetrazolium chloride and cresyl violet staining, respectively. We found that an exposure to environmental enrichment was associated with higher post-ischemic cerebral blood flow and less brain tissue loss in the ipsilesional primary somatosensory cortex compared with the standard cage environment. Furthermore, environmental enrichment also enhanced the cerebral blood flow response to whisker stimulation in the ipsilesional barrel cortex when measured 28 days after the middle cerebral artery occlusion. Together, the data suggested that an exposure to environmental enrichment promoted the restoration of cerebral blood flow in the ipsilesional cortex and contributed to a better coupling between functional activation and cerebral blood flow change, which might be the possible mechanisms underlying the neuroprotective effects of EE after ischemia.

Altered resting-state functional networks in patients with hemodialysis: a graph-theoretical based study.

Recent studies have demonstrated that hemodialysis patients exhibit disruptions in functional networks with invisible cerebral alterations. We explored the alterations of functional connectivity in hemodialysis patients using the graph-theory method. A total of 46 hemodialysis patients (53.11 ± 1.58 years, 28 males) and 47 healthy controls (55.57 ± 0.86 years, 22 males) were scanned byusing resting-state functional magnetic resonance imaging. The brains of these patients were divided into 90 regions and functional connectivity was constructed with the automatic anatomical labeling atlas. In the defined threshold range, the graph-theory analysis was performed to compare the topological properties including global, regional and edge parameters between the hemodialysis and the healthy control groups. Both hemodialysis patients and healthy control subjects demonstrated common small-world property of the brain functional connections. At the global level, the parameters normalized clustering coefficients and small-worldness were significantly decreased in hemodialysis patients compared with those noted in healthy controls. At the regional level, abnormal nodal metrics (increased or decreased nodal degree, betweenness centrality and efficiency) were widely found in hemodialysis patients compared with those of healthy controls. The network-based statistical method was employed and two disrupted neural circuits with 18 nodes and 19 edges (P = 0.0139, corrected) and 10 nodes and 11 edges (P = 0.0399, corrected) were detected. Of note, the edge-increased functional connectivity was associated with the salience network and the frontal-temporal-basal ganglia connection, whereas the edge-decreased functional connectivity was associated with the frontoparietal network. The graph-theory method may be one of the potential tools to detect disruptions of cerebral functional connectivity and provide important evidence for understanding the neuropathology of hemodialysis patients from the disrupted network organization perspective.

Cerebral regional and network characteristics in asthma patients: a resting-state fMRI study.

Asthma is a serious health problem that involves not only the respiratory system but also the central nervous system. Previous studies identified either regional or network alterations in patients with asthma, but inconsistent results were obtained. A key question remains unclear: are the regional and neural network deficits related or are they two independent characteristics in asthma? Answering this question is the aim of this study. By collecting resting-state functional magnetic resonance imaging from 39 patients with asthma and 40 matched health controls, brain functional measures including regional activity (amplitude of low-frequency fluctuations) and neural network function (degree centrality (DC) and functional connectivity) were calculated to systematically characterize the functional alterations. Patients exhibited regional abnormities in the left angular gyrus, right precuneus, and inferior temporal gyrus within the default mode network. Network abnormalities involved both the sensorimotor network and visual network with key regions including the superior frontal gyrus and occipital lobes. Altered DC in the lingual gyrus was correlated with the degree of airway obstruction. This study elucidated different patterns of regional and network changes, thereby suggesting that the two parameters reflect different brain characteristics of asthma. These findings provide evidence for further understanding the potential cerebral alterations in the pathophysiology of asthma.

Novel Control Mechanism of the Neurovascular Coupling in an Alzheimer’s Disease Model

Alzheimer’s disease (AD) is a type of dementia related to age characterized by a progressive and irreversible deterioration of memory and general cognitive abilities. There is a consensus that the production of β‐amyloid protein (Aβ) aggregates correlates with neuronal alterations, triggering the characteristic neurodegeneration process of this disease. Furthermore, disease progression has been closely associated with cerebral vascular alterations, such as reduction in cerebral blood flow observed in patients and animal models of AD.It has been documented that Aβ not only has harmful effects at neuronal level but has also been associated with the alteration of astrocytes normal activity. One of the events modulated by astrocytes at cerebral level is its key role in the neurovascular coupling (NVC), mechanism that ensures nutrients and oxygen supply in proportion to the increase in neuronal activity. The NVC functions controlled by the astrocytes is mediated by vasodilator signals, a process that is dependent of intracellular calcium increase in astrocytes, which is propagated and coordinated by the release of paracrine and autocrine adenosine triphosphate (ATP).There is no consensus about the way of ATP release from astrocytes during NVC, but the description of a new channel, Calcium Homeostasis Modulator 1 (CALHM1) which permit the ATP release in some type of neurons, could be an important element in astrocyte signaling during this mechanism. In previous results we observed that ATP is released through CALHM1 in an astrocyte primary culture model stimulated with glutamate (a stimulus validated in NVC studies) and also was dependent of the CALHM1 activation by S‐nitrosylation through nitric oxide (NO) produced by the astrocytes.Considering that it has been reported that NVC is altered in AD, which contribute to the pathophysiological mechanisms of this disease, our main aim was to evaluate the ATP release in astrocytes primary cultures from a validated murine model of AD: B6C3‐Tg(APPswe,PSEN1dE9)85Dbo/Mmjax.Our results show that ATP release, and CALHM1 relative levels and expression are significatively reduced in astrocytes primary cultures from AD animals in comparing with cultures from wild type animals. These results suggest that calcium signaling could be diminished in the astrocytes in AD and could explicate the relation between the alteration of NVC in AD.Support or Funding InformationUniversidad del Desarrollo Intern Proyect 23.400.163

The functional alterations in primary migraine: A systematic review and meta-analysis protocol.

Introduction:Accumulating neuroimaging studies have found abnormal cerebral activity in migraine patients. However, the findings of studies exist many differences. Hence, this protocol aims to investigate concurrence across the neuroimaging studies to verify the functional cerebral alterations based on the latest evidence.Methods and analysis:Functional neuroimaging studies comparing migraineur with healthy subjects will be searched in the 4 online databases (EMBASE, the Cochrane Library, PubMed, and Web of Science) up to June 2019. The selection of studies, quality assessment, and data extraction will be conducted by 2 independent researchers. The Anisotropic effect size version of signed differential mapping (AES-SDM) methods will be used to conduct a coordinate-based meta-analysis. The bias of publication will be confirmed via the P value of Egger test. The quality of studies will be evaluated by the Newcastle-Ottawa Scale (NOS). This study is registered with PROSPERO, number CRD42019129043.Results:This study will deepen the understanding of functional cerebral alterations of migraine.Conclusion:The study will provide clear conclusion of the functional cerebral alterations based on the latest evidence.

Extracellular Vesicles from Hyperammonemic Rats Induce Neuroinflammation and Motor Incoordination in Control Rats.

Minimal hepatic encephalopathy is associated with changes in the peripheral immune system which are transferred to the brain, leading to neuroinflammation and thus to cognitive and motor impairment. Mechanisms by which changes in the immune system induce cerebral alterations remain unclear. Extracellular vesicles (EVs) seem to play a role in this process in certain pathologies. The aim of this work was to assess whether EVs play a role in the induction of neuroinflammation in cerebellum and motor incoordination by chronic hyperammonemia. We characterized the differences in protein cargo of EVs from plasma of hyperammonemic and control rats by proteomics and Western blot. We assessed whether injection of EVs from hyperammonemic to normal rats induces changes in neuroinflammation in cerebellum and motor incoordination similar to those exhibited by hyperammonemic rats. We found that hyperammonemia increases EVs amount and alters their protein cargo. Differentially expressed proteins are mainly associated with immune system processes. Injected EVs enter Purkinje neurons and microglia. Injection of EVs from hyperammonemic, but not from control rats, induces motor incoordination, which is mediated by neuroinflammation, microglia and astrocytes activation and increased IL-1β, TNFα, its receptor TNFR1, NF-κB in microglia, glutaminase I, and GAT3 in cerebellum. Plasma EVs from hyperammonemic rats carry molecules necessary and sufficient to trigger neuroinflammation in cerebellum and the mechanisms leading to motor incoordination.

Neuroimaging in Vascular Cognitive Impairment and Dementia: A Systematic Review.

Cerebrovascular diseases are well established causes of cognitive impairment. Different etiologic entities, such as vascular dementia (VaD), vascular cognitive impairment, subcortical (ischemic) VaD, and vascular cognitive disorder, are included in the umbrella definition of vascular cognitive impairment and dementia (VCID). Because of the variability of VCID clinical presentation, there is no agreement on criteria defining the neuropathological threshold of this disorder. In fact, VCID is characterized by cerebral hemodynamic alteration which ranges from decreased cerebral blood flow to small vessels disease and involves a multifactorial process that leads to demyelination and gliosis, including blood-brain barrier disruption, hypoxia, and hypoperfusion, oxidative stress, neuroinflammation and alteration on neurovascular unit coupling, cerebral microbleeds, or superficial siderosis. Numerous criteria for the definition of VaD have been described: the National Institute of Neurological Disorders and Stroke Association Internationale pour Recherche'-et-l'Enseignement en Neurosciences criteria, the State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria, DSM-V criteria, the Diagnostic Criteria for Vascular Cognitive Disorders (a VASCOG Statement), and Vascular Impairment of Cognition Classification Consensus Study. Neuroimaging is fundamental for definition and diagnosis of VCID and should be used to assess the extent, location, and type of vascular lesions. MRI is the most sensible technique, especially if used according to standardized protocols, even if CT plays an important role in several conditions. Functional neuroimaging, in particular functional MRI and PET, may facilitate differential diagnosis among different forms of dementia. This systematic review aims to explore the state of the art and future perspective of non-invasive diagnostics of VCID.

V2O5 Nanobelts Mimick Tandem Enzymes To Achieve Nonenzymatic Online Monitoring of Glucose in Living Rat Brain.

The continuous detection of glucose is significant for revealing its role in neuron protection and for diagnosis of various diseases. In this study, for the first time, a nonenzymatic online optical detection platform (OODP) for glucose measurement in rat brain utilizing the tandem enzyme activity of V2O5 nanobelts is developed. V2O5 nanobelts were synthesized via a facile solvothermal strategy, and for the first time it is found that the V2O5 nanobelts possess dual enzyme-like activity, i.e., glucose oxidase (GOx)-like and peroxidase-like activity, and can act as a "tandem nanozyme". To investigate the mechanisms of the GOx-like property, we built an adsorption model, and the RPBE density functional calculations indicate that the glucose molecule can be adsorbed on the V2O5 plane. Based on the ability of V2O5 nanobelts to mimick tandem enzymes, a nonenzymatic online optical detection platform (OODP) for the continuous monitoring of glucose in rat brain was designed, which exhibits excellent stability, high selectivity, and a wide linear detection range from 0.2 to 5 mM and records cerebral glucose alterations in the calm/ischemia model. This facile but reliable nonenzymatic online optical glucose measurement compares favorably with natural enzyme-based online electrochemical glucose analytical systems, and its ready adoption by physiologists and pathologists will facilitate the understanding of brain function and the pathogenesis of diabetes.

Left cerebral cortex complexity differences in sporadic healthy individuals with auditory verbal hallucinations: A pilot study

In the present pilot study, we aimed to characterize the brain surface differences between 42 sporadic healthy individuals with AVHs (Hi-AVHs) and 50 healthy individuals without AVHs. The Auditory Hallucinations Rating Scale (AHRS) was used to assess the severity of AVHs, while the gyrification index and fractal dimensions were used to evaluate cerebral cortex complexity. We observed a significant increase of the gyrification index was located in the left superior temporal gyrus, the left temporoparietal junction, the left superior frontal gyrus, and the left parietal lobe. The fractal dimensions had significantly increased in the left Wernicke's area, the left Broca's areas and the left parietal lobe. Our pilot findings indicated gyrification index and fractal dimensions differences were only located in the left hemisphere between the groups of Hi-with and without AVHs. However, these differences did not correlate with the AVHs symptoms, and the non-hallucinating healthy individuals did not demonstrate corresponding reverse changes; hence we cannot postulate that cerebral cortex complexity alterations are related to AVHs. Our pilot study provides a clue for further studies aimed at investigating the brain features of Hi-AVHs.

Acute Effects of Whole-Body Vibration on Dopplerfluxometry of the Common Carotid Artery Parameters among Adult and Elderly Non-Athletes Healthy Dogs

Background: Whole-Body Vibration (WBV) is an oscillatory mechanical stimulus spreading throughout the body and considered a type of physical exercise because of the activation of the cardiovascular, musculoskeletal, and neuroendocrine systems. It is a physical exercise modality since it promotes cardiovascular resistance, increase in muscular strength and neurosensitivity, and motor coordination improvement. For use of WBV as an exercise modality for dogs, it is necessary to evaluate the Dopplerfluxometry parameters of the common carotid artery in healthy dogs in order to perform a safe protocol without inducing any cerebral alteration. This study aimed to evaluate the acute effects of WBV on systolic peak velocity (SPV), resistivity (RI), and pulsatility index (PI) of the both common carotid artery among adults and elderly non-athletes healthy dog.Materials, Methods &amp; Results: Fourteen clinically healthy, neutered crossbreed male dogs, non-athlete were divided into two groups of seven dogs, according to the age group: Group 1 (G1)- Adult dogs: age between 12 and 84 months; Group 2 (G2)- Elderly dogs: aged over 84 months. All dogs were submitted to sessions of WBV using the protocol of 30 Hz for 5 min, followed by an increase to 50 Hz for 5 more min and ending with 5 min at 30 Hz, without rest between the variation of the vibration frequency. The systolic peak velocity (SPV), resistivity (RI), and pulsatility index (PI) of the common carotid artery were assessed in two time-points: 5 min before the WBV sessions (5PRE) and 1 min after the WBV (1POS). No significant variations in the SPS, RI, and PI of both common carotid artery of the G1 and G2 were identified. The anatomic reference for the left and right common carotid artery was the right and left extern jugulars veins, which were identified by the venous blood vessel characteristics as endothelium type, and single-phase without systolic peaks wave. Discussion: In humans, WBV is indicated to muscle size and tone increase, therefore it is believed that this modality can present a beneficial result in dogs with muscular atrophy associated with orthopedic surgeries and in cases of osteoarthritis. Irreversible brain damage can be caused by a possible hemodynamic alteration in the common carotid arteries resulted from mechanical vibrations. Parkinson’s disease patients and individuals affected by strokes that went under acute sessions of WBV showed handshake reduction and better proprioception, respectively. The beneficial effect was observed in cervix opening in dogs with metritis. The behavior of sitting of the dogs over 30 kg during WBVsessions was associated with paraparesis. This result was present in medium-size non-athletic dogs weighing from 10.1 to 17.9 kg that went through WBV for 5 consecutive days, using the same vibrating platform. No signs of discomfort during a single session of 10 min of WBV (15 and 21 Hz) were observed in healthy adult horses. Studies using mechanical vibrations on adult healthy dogs did not show significant variation RI of the renal artery. On the other hand, daily use of WBV for 5 days on dogs showed significant enhancement on RI of the femoral artery immediately after it. A single session of WBV (30 and 50 Hz did, for 15 min) do not produce undesirable effects on SPV, RI, and PI of both common carotid arteries in adult and elderly non-athletic healthy dogs.

Eyeballing stroke: Blood flow alterations in the eye and visual impairments following transient middle cerebral artery occlusion in adult rats

Middle cerebral artery occlusion in rodents remains a widely used model of ischemic stroke. Recently, we reported the occurrence of retinal ischemia in animals subjected to middle cerebral artery occlusion, owing in part to the circulatory juxtaposition of the ophthalmic artery to the middle cerebral artery. In this study, we examined the eye hemodynamics and visual deficits in middle cerebral artery occlusion-induced stroke rats. The brain and eye were evaluated by laser Doppler at baseline (prior to middle cerebral artery occlusion), during and after middle cerebral artery occlusion. Retinal function-relevant behavioral and histological outcomes were performed at 3 and 14 days post-middle cerebral artery occlusion. Laser Doppler revealed a typical reduction of at least 80% in the ipsilateral frontoparietal cortical area of the brain during middle cerebral artery occlusion compared to baseline, which returned to near-baseline levels during reperfusion. Retinal perfusion defects closely paralleled the timing of cerebral blood flow alterations in the acute stages of middle cerebral artery occlusion in adult rats, characterized by a significant blood flow defect in the ipsilateral eye with at least 90% reduction during middle cerebral artery occlusion compared to baseline, which was restored to near-baseline levels during reperfusion. Moreover, retinal ganglion cell density and optic nerve depth were significantly decreased in the ipsilateral eye. In addition, the stroke rats displayed eye closure. Behavioral performance in a light stimulus-mediated avoidance test was significantly impaired in middle cerebral artery occlusion rats compared to control animals. In view of visual deficits in stroke patients, closely monitoring of brain and retinal perfusion via laser Doppler measurements and examination of visual impairments may facilitate the diagnosis and the treatment of stroke, including retinal ischemia.

Focal alterations of the callosal area III in primary lateral sclerosis: An MRI planimetry and texture analysis.

The regional distribution of cerebral morphological alterations in primary lateral sclerosis (PLS) is considered to include the area III of the corpus callosum (CC). The study was designed to investigate regional white matter (WM) alterations in the callosal area III by T1 weighted magnetic resonance imaging (T1w-MRI) data in PLS patients compared with healthy controls, in order to identify atrophy and texture changes in vivo. T1w-MRI-based white matter mapping was used to perform an operator-independent CC-segmentation for the different areas of the CC in 67 PLS patients vs 82 matched healthy controls and vs 85 ALS patients. The segmentation was followed by texture analysis of the separated CC areas for the PLS patients vs controls and vs ALS patients. PLS was associated with significant atrophy in the area III of the CC (but not in the other callosal segments), while the alterations in the ALS patients were much more variable and were not significant at the group level. Furthermore, significant regional alterations of the texture parameters entropy and homogeneity in this area were shown in PLS patients and in ALS patients. This T1w-MRI study demonstrated focused regional CC atrophy and texture alterations limited to the callosal area III (which comprises fibers projecting into the primary motor cortices) in PLS, in comparison to a higher variability in CC size in ALS.

Manipulation of microbiota with probiotics as an alternative for treatment of hepatic encephalopathy.

Hepatic encephalopathy is a cerebral alteration mainly caused by hepatic insufficiency or portosystemic shunt. It ranges from minimal neurologic manifestations to coma in its overt stage. The multifactorial pathophysiology of hepatic encephalopathy has rendered numerous treatment alternatives, among which the modification of dysbiosis and hyperammonemia are currently considered to be effective, not only clinically, but also regarding cost. Recent work has developed knowledge of probiotics in different clinical settings including the relationship of the gut microenvironment to liver cirrhosis. The aim of this review was to analyze the results of clinical trials on the effect of different probiotics on hepatic encephalopathy.

A novel computer-aided diagnosis system for the early detection of hypertension based on cerebrovascular alterations.

Hypertension is a leading cause of mortality in the USA. While simple tools such as the sphygmomanometer are widely used to diagnose hypertension, they could not predict the disease before its onset. Clinical studies suggest that alterations in the structure of human brains' cerebrovasculature start to develop years before the onset of hypertension. In this research, we present a novel computer-aided diagnosis (CAD) system for the early detection of hypertension. The proposed CAD system analyzes magnetic resonance angiography (MRA) data of human brains to detect and track the cerebral vascular alterations and this is achieved using the following steps: i) MRA data are preprocessed to eliminate noise effects, correct the bias field effect, reduce the contrast inhomogeneity using the generalized Gauss-Markov random field (GGMRF) model, and normalize the MRA data, ii) the cerebral vascular tree of each MRA volume is segmented using a 3-D convolutional neural network (3D-CNN), iii) cerebral features in terms of diameters and tortuosity of blood vessels are estimated and used to construct feature vectors, iv) feature vectors are then used to train and test various artificial neural networks to classify data into two classes; normal and hypertensive. A balanced data set of 66 subjects were used to test the CAD system. Experimental results reported a classification accuracy of 90.9% which supports the efficacy of the CAD system components to accurately model and discriminate between normal and hypertensive subjects. Clinicians would benefit from the proposed CAD system to detect and track cerebral vascular alterations over time for people with high potential of developing hypertension and to prepare appropriate treatment plans to mitigate adverse events.

An Observational Cerebral Magnetic Resonance Imaging Study Following 7 Days at 4554 m.

Background: In human beings exposed to high altitude, cerebral magnetic resonance imaging (cMRI) revealed alterations ranging from subclinical cerebral edema formation to subtle brain abnormalities. Yet, brain structure after adaptation to high altitude and their recovery after return to lowlands have been rarely investigated. We, therefore, examined 10 healthy individuals by cMRI before, 12 hours after descent (R + 12h), and again 3.5 months (R + 3.5m) after a 7-day high altitude exposure at 4554 m. Results: After their 3-day lasting, stepwise ascent to 4554 m, all subjects suffered acute mountain sickness with a mean Lake Louise score of 5.8 ± 1.7 after the first night at that altitude. Acute mountain sickness completely resolved after 4 days at 4554 m. While 12 hours after descent mean white and gray matter volumes were increased compared with before altitude exposure (p = 0.045 and p = 0.002), these volumes were normalized on R + 3.5m. Moreover, we observed significant focal volume alterations likely attributed to either vasogenic or cytotoxic edema formation. Two subjects presented new brain findings after altitude exposure. In one individual the number of preexisting white matter hyperintensities (WMHI) transiently increased, in the other individual a reversible splenial lesion syndrome (RESLES) emerged. Both findings had resolved 15 and 8 days after descent, respectively. None developed structural lesions like brain atrophy, cerebral infarcts, microbleeds, or high-altitude cerebral edema. Discussion: Three days after complete recovery from acute mountain sickness and after return to low altitude, subclinical vasogenic and cytotoxic edema, RESLES and WMHI are present in high-altitude acclimatized individuals. However, these cerebral alterations are reversible within months at lowland.

NIMG-31. BRAIN CONNECTIVITY PATTERNS CHARACTERIZE COGNITIVE IMPAIRMENT IN LONG-TERM SURVIVORS OF LOW-GRADE GLIOMA (LGG) USING RESTING-STATE FUNCTIONAL MRI (rs-fMRI)

Abstract Advanced multimodality treatments that have led to longer survival rates for patients with low-grade gliomas (LGGs) have also resulted in significant changes in cognition and quality of life (QoL). These changes remain poorly understood, largely due to the lack of multifactorial and in-depth studies on cognitive impairment in patients with LGG. Resting-state functional MRI (rs-fMRI) has been widely used as a reliable imaging biomarker to evaluate the treatment outcome by characterizing the cerebral networking alteration associated with a patient’s neurological status. In this preliminary report of an active study, we investigated the cognitive function and cerebral networking connectivity via rs-fMRI in survivors who had completed treatment for LGG within the past 10 years. Survivors were administered a battery of standardized neuropsychological tests. Of the 20 participants enrolled to date (mean age 43 ± 11), 10 participants were categorized as cognitively impaired based on the International Cognition and Cancer Task Force (ICCTF) guidelines, with recommended adjustments considering the number of tests in the battery. Compared to cognitively unimpaired participants, functional connectivity in cognitively impaired patients was lower between memory, visuospatial processing, and primary sensorimotor regions. These preliminary observations suggest there is a potential link between overall cognitive impairment and functional connectivity of various networks as measured using resting-state fMRI.