Cerebrovascular Alterations Research Articles

Key brain cell interactions and contributions to the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, with the two major hallmarks being the deposition of extracellular β-amyloid (Aβ) plaques and of intracellular neurofibrillary tangles (NFTs). Additionally, early pathological events such as cerebrovascular alterations, a compromised blood-brain barrier (BBB) integrity, neuroinflammation and synaptic dysfunction, culminate in neuron loss and cognitive deficits. AD symptoms reflect a loss of neuronal circuit integrity in the brain; however, neurons do not operate in isolation. An exclusively neurocentric approach is insufficient to understand this disease, and the contribution of other brain cells including astrocytes, microglia, and vascular cells must be integrated in the context. The delicate balance of interactions between these cells, required for healthy brain function, is disrupted during disease. To design successful therapies, it is critical to understand the complex brain cellular connections in AD and the temporal sequence of their disturbance. In this review, we discuss the interactions between different brain cells, from physiological conditions to their pathological reactions in AD, and how this basic knowledge can be crucial for developing new therapeutic strategies.

Cerebral angiography as a tool for diagnosis and management of idiopathic intracranial hypertension syndrome

PurposeIdiopathic intracranial hypertension syndrome (IIH) is a pathology characterized by headache, visual disturbances, papilledema, increased cerebrospinal fluid pressure with normal cytochemistry that is not attributable to cerebral structural alterations. This study aimed to describe the usefulness of cerebral angiography in the diagnostic approach and management of patients with clinical suspicion of IIH at a fourth level hospital in Cali, Colombia. MethodsThis was a retrospective study. Patients diagnosed with IIH at the hospital [Blinded], Cali, Colombia, from October 2013 to May 2018 were included. Their medical records were reviewed, and clinical and diagnostic variables were collected along with outcomes and follow-up data. ResultsA series of 13 cases, 12 women and 1 man, between the second and fifth decade of life, with an average age of 29.4 years were included. All presented with headache; 12 had papilledema (92%), and diplopia and palsy of cranial nerve VI were observed in 3 cases (46%). All patients underwent simple CT scan of the brain and simple and gadolinium-enhanced MRI of the brain, none of which showed lesions that would explain the intracranial hypertension; however, upon resonance angiography followed by cerebral angiography, 8 cases (61%) of cerebral venous sinus involvement were found. ConclusionPatients who present with a clinical picture compatible with IIH should undergo intra-arterial digital subtraction angiography (IADSA) to rule out cerebrovascular alterations.

Increased Neurovascular Vulnerability to Mild Traumatic Brain Injury in a Mouse Model of Marfan Syndrome

Over 69 million traumatic brain injuries (TBIs) are reported annually worldwide, where the geriatric population are at greatest risk for prolonged morbidity and mortality. Cerebrovascular aging contributes to this increased vulnerability through extracellular matrix (ECM) impairment, vascular wall weakening and stiffening, blood‐brain barrier (BBB) permeability, and exacerbated cytokine production, yet the mechanisms behind these contributions are minimally investigated. In order to study these targets efficiently and with minimal variability, an animal model presenting these cerebrovascular alterations is required. Fibrillin‐1 (Fbn1) protein plays a role in elasticity and inflammation, and its mutation is known to lead to ECM impairment and vessel wall weakening induced by increased availability in transforming growth factor‐b (TGF‐b) and downstream production of matrix metalloproteinases (MMPs)‐2/‐9. In mice, this mutation induces vascular dysfunction by 6M of age and is a well‐established model of Marfan Syndrome.In this study, Fbn1+/‐ were utilized to test the hypothesis that Fbn1 mutation accelerates cerebrovascular rigidity, BBB permeability, and neurological alterations associated with aging, leaving the brain more vulnerable to diffuse TBI. In 6M‐ and 12M‐old Fbn1+/‐ and C57BL/6 wildtype (WT) male and female mice, posterior cerebral artery (PCA) blood flow (n=8‐10), PCA rupture point (N=3‐5/group), BBB permeability (N=2‐3/group), injury viability (N=5‐8/group), neurobehavioral severity scale (NSS) outcomes (N=10‐11/group), and microglial perturbation (N=1/group) were assessed.Our data shows that 6M‐old Fbn1+/‐ mice have decreased PCA blood flow (p<0.05), compromised PCA wall strength (p<0.05), increased BBB permeability (p<0.05), and elevated NSS scores (p<0.05) as compared to 6M‐old WT, and similar to 12M‐old WT mice. Preliminary investigation of iba‐1 staining for microglia, a supported assessment of neuroinflammation, suggests increased microglial activation in 6M‐old Fbn1+/‐ mice compared to age‐matched WT mice. To investigate vulnerability to mild TBI (mTBI), varying pulse pressures (1.11‐1.32atm) were applied to the brains of 6M‐old WT (1.25‐1.32atm) and Fbn1+/‐ (1.17‐1.21atm) mice using midline fluid percussion injury, where Fbn1+/‐ mice required lowered pressure to induce mTBI righting reflex times (5‐10 minutes).These data support that cerebrovascular aging contributes to outcome after TBI. Furthermore, this study demonstrates that Fbn1 mutation plays a critical role in the vulnerability of the aged brain to mTBI. Using this novel approach of a Marfan Syndrome mouse model that isolates cerebrovascular aging allows for the mechanistic study of potential Fbn1 downstream pathways that could serve as a therapeutic target for prevention and management of post‐concussive symptoms.

Endothelial BACE1 Impairs Cerebral Small Vessels via Tight Junctions and eNOS.

Cerebral small vessel injury, including loss of endothelial tight junctions, endothelial dysfunction, and blood-brain barrier breakdown, is an early and typical pathology for Alzheimer's disease, cerebral amyloid angiopathy, and hypertension-related cerebral small vessel disease. Whether there is a common mechanism contributing to these cerebrovascular alterations remains unclear. Studies have shown an elevation of BACE1 (β-site amyloid precursor protein cleaving enzyme 1) in cerebral vessels from cerebral amyloid angiopathy or Alzheimer's disease patients, suggesting that vascular BACE1 may involve in cerebral small vessel injury. To understand the contribution of vascular BACE1 to cerebrovascular impairments, we combined cellular and molecular techniques, mass spectrometry, immunostaining approaches, and functional testing to elucidate the potential pathological mechanisms. We observe a 3.71-fold increase in BACE1 expression in the cerebral microvessels from patients with hypertension. Importantly, we discover that an endothelial tight junction protein, occludin, is a completely new substrate for endothelial BACE1. BACE1 cleaves occludin with full-length occludin reductions and occludin fragment productions. An excessive cleavage by elevated BACE1 induces membranal accumulation of caveolin-1 and subsequent caveolin-1-mediated endocytosis, resulting in lysosomal degradation of other tight junction proteins. Meanwhile, membranal caveolin-1 increases the binding to eNOS (endothelial nitric oxide synthase), together with raised circulating Aβ (β-amyloid peptides) produced by elevated BACE1, leading to an attenuation of eNOS activity and resultant endothelial dysfunction. Furthermore, the initial endothelial damage provokes chronic reduction of cerebral blood flow, blood-brain barrier leakage, microbleeds, tau hyperphosphorylation, synaptic loss, and cognitive impairment in endothelial-specific BACE1 transgenic mice. Conversely, inhibition of aberrant BACE1 activity ameliorates tight junction loss, endothelial dysfunction, and memory deficits. Our findings establish a novel and direct relationship between endothelial BACE1 and cerebral small vessel damage, indicating that abnormal elevation of endothelial BACE1 is a new mechanism for cerebral small vessel disease pathogenesis.

Magnetic Resonance Imaging in Animal Models of Alzheimer's Disease Amyloidosis.

Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

Hemiballism a Case Report and Literature Review

The term ballism derives from the Greek word ballistēs which translates as throw. Ballism is one of the abnormal movements reported in the medical literature, characterized by the involuntary, non-purposeful action of a limb, in a repetitive, sudden, centrifugal way, and when it affects the upper and lower limbs together ipsilaterally in a patient is called hemiballism, this neurological manifestation is part of the so-called abnormal hyperkinetic movements. The objective of our report is to present the clinical picture of a patient with hemiballism who jointly presents cerebrovascular alterations and the use of dopaminergic drugs. He is a male of 79 years old, with a history of chronic degenerative diseases such as, systemic hypertension, diabetes mellitus type II, cerebrovascular disease, hyperlipidemia, vascular cognitive deficit and apparently Parkinson's disease, which presented abnormal movements of sudden onset, of insidious progression, to the left side of the uncoordinated type, abrupt, thick, centrifugal, causing disability in their bodily functioning and deteriorating their quality of life. This picture began after the increase in the medicines used for the diagnosis of Parkinson's disease. The diagnosis of Hemiballism was established and medical treatment based on Haloperidol and reduction of the antiparkinsonic drug was provided, showing an important improvement evidenced in the attached video. A review of the anatomical, histological, physiological and pathophysiological aspects related to this type of pathology is made emphasizing the relationship of the direct and indirect pathways of the extrapyramidal system used for the modulation of the corporal movement by the primary motor system.

Cerebrovascular alterations in NAFLD: Is it increasing our risk of Alzheimer's disease?

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, which has been classified as an emerging epidemic not only confined to liver-related morbidity and mortality. It is also becoming apparent that NAFLD is associated with moderate cerebral dysfunction and cognitive decline. A possible link between NAFLD and Alzheimer's disease (AD) has only recently been proposed due to the multiple shared genes and pathological mechanisms contributing to the development of these conditions. Although AD is a progressive neurodegenerative disease, the exact pathophysiological mechanism remains ambiguous and similarly to NAFLD, currently available pharmacological therapies have mostly failed in clinical trials. In addition to the usual suspects (inflammation, oxidative stress, blood-brain barrier alterations and ageing) that could contribute to the NAFLD-induced development and progression of AD, changes in the vasculature, cerebral perfusion and waste clearance could be the missing link between these two diseases. Here, we review the most recent literature linking NAFLD and AD, focusing on cerebrovascular alterations and the brain's clearance system as risk factors involved in the development and progression of AD, with the aim of promoting further research using neuroimaging techniques and new mechanism-based therapeutic interventions.

Involvement of cerebrovascular abnormalities in the pathogenesis and progression of Alzheimer's disease: an adrenergic approach.

Alzheimer’s disease (AD), as the most common neurodegenerative disease in elder population, is pathologically characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles composed of highly-phosphorylated tau protein and consequently progressive neurodegeneration. However, both Aβ and tau fails to cover the whole pathological process of AD, and most of the Aβ- or tau-based therapeutic strategies are all failed. Increasing lines of evidence from both clinical and preclinical studies have indicated that age-related cerebrovascular dysfunctions, including the changes in cerebrovascular microstructure, blood-brain barrier integrity, cerebrovascular reactivity and cerebral blood flow, accompany or even precede the development of AD-like pathologies. These findings may raise the possibility that cerebrovascular changes are likely pathogenic contributors to the onset and progression of AD. In this review, we provide an appraisal of the cerebrovascular alterations in AD and the relationship to cognitive impairment and AD pathologies. Moreover, the adrenergic mechanisms leading to cerebrovascular and AD pathologies were further discussed. The contributions of early cerebrovascular factors, especially through adrenergic mechanisms, should be considered and treasured in the diagnostic, preventative, and therapeutic approaches to address AD.

MRI-Based Investigation of Association Between Cerebrovascular Structural Alteration and White Matter Hyperintensity Induced by High Blood Pressure.

High blood pressure (BP) is a common risk factor for cerebral small vessel disease including white matter hyperintensity (WMH). Whether increased BP exacerbates WMH by impacting cerebral vascular morphologies remains poorly studied. To determine the relationships among high BP, cerebrovascular morphologies, and WMH in elderly individuals. Cohort. Eight hundred sixty-three participants (54.2% female) from the Taizhou Imaging Study without clinical evidence of neurologic disorders were included in the analyses. 3.0 T; time-of-flight magnetic resonance angiography (TOF MRA); T2 fluid-attenuated inversion recovery (FLAIR); T1 magnetization-prepared rapid gradient-echo; gradient echo T2*-weighted; diffusion tensor imaging; pulsed arterial spin labeling. Cerebrovascular morphologic measurements were quantified based on the TOF MRA images, including vessel density, radius, tortuosity, and branch number. WMH lesion volumes (WMHV) and WMH lesion counts (WMHC) were calculated automatically based on the T2 FLAIR images. Multivariable linear regression analysis and path analysis with a linear single-mediator model were employed. A P value <0.05 was considered statistically significant. Higher BP, especially diastolic BP, was significantly correlated with lower cerebrovascular density (β=-104) and lower branch numbers (β=-0.02). Although decreased tortuosity (β=-1.25) and increased radius (β=93.8) were correlated with BP, no significant relationship of tortuosity (β=-4.6 × 10-4 , P=0.58) or radius (β=0.03, P=0.08) with BP in small vessels was found. The proportion of small vessels decreased as BP increased (SBP: β=-6.6 × 10-4 ; DBP: β=-9.0 × 10-4 ). Similarly, increased WMHV and WMHC were associated with decreased vessel density (volumes: β=-24, counts: β=-127), decreased tortuosity (volumes: β=-0.08, counts: β=-0.53), and increased radius (volumes: β=12.6, counts: β=86.6). Path analyses suggested an association between high BP and WMHs that were mediated by cerebrovascular morphologic changes. Structural alterations of cerebral vessels induced by high BP are correlated with WMH. This result suggested that elevated BP might be one of the pathophysiological mechanisms involving in the co-occurrence of cerebrovascular alteration and small vessel disease. 1 Technical Efficacy Stage: 1.

Exercise intolerance in pulmonary arterial hypertension: insight into central and peripheral pathophysiological mechanisms.

Exercise intolerance is a cardinal symptom of pulmonary arterial hypertension (PAH) and strongly impacts patients' quality of life (QoL). Although central cardiopulmonary impairments limit peak oxygen consumption (V' O2peak ) in patients with PAH, several peripheral abnormalities have been described over the recent decade as key determinants in exercise intolerance, including impaired skeletal muscle (SKM) morphology, convective O2 transport, capillarity and metabolism indicating that peripheral abnormalities play a greater role in limiting exercise capacity than previously thought. More recently, cerebrovascular alterations potentially contributing to exercise intolerance in patients with PAH were also documented. Currently, only cardiopulmonary rehabilitation has been shown to efficiently improve the peripheral components of exercise intolerance in patients with PAH. However, more extensive studies are needed to identify targeted interventions that would ultimately improve patients' exercise tolerance and QoL. The present review offers a broad and comprehensive analysis of the present literature about the complex mechanisms and their interactions limiting exercise in patients and suggests several gaps in knowledge that need to be addressed in the future for a better understanding of exercise intolerance in patients with PAH.

Association between neurofibromatosis type 1 and cerebrovascular diseases in children: A systematic review.

BackgroundNeurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular damage. Although not commonly recognized in the context of NF-1, cerebrovascular disease (CVD), can be often present since childhood and diagnosed just later in life. When present, NF-1-associated CVD clinical manifestations may include headache, cognitive deficits and ultimately aneurysm rupture, causing death. Thus, CVD plays an important role in the clinical manifestations, disease severity and prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD in children.MethodsTwo independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: “neurofibromatosis type 1”, “Von Recklinghausen’s disease”, "children", "adolescents", "stroke", "Moyamoya disease", "vascular diseases", "cerebrovascular disorders", "aneurysm" and "congenital abnormalities". Studies focused on assessing the development of CVD in children with NF-1 were included.ResultsSeven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic.ConclusionThe available evidence suggests that CVDs are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, improved prognosis was observed when imaging tests were performed to screen for cerebrovascular alterations early during the clinical investigation. Early diagnosis of CVD in NF-1 patients foster implementation of timely interventions, directly impacting clinical outcomes.

Intact in vivo visualization of telencephalic microvasculature in medaka using optical coherence tomography

To date, various human disease models in small fish—such as medaka (Oryzias lapties)—have been developed for medical and pharmacological studies. Although genetic and environmental homogeneities exist, disease progressions can show large individual differences in animal models. In this study, we established an intact in vivo angiographic approach and explored vascular networks in the telencephalon of wild-type adult medaka using the spectral-domain optical coherence tomography. Our approach, which required neither surgical operations nor labeling agents, allowed to visualize blood vessels in medaka telencephala as small as about 8 µm, that is, almost the size of the blood cells of medaka. Besides, we could show the three-dimensional microvascular distribution in the medaka telencephalon. Therefore, the intact in vivo imaging via optical coherence tomography can be used to perform follow-up studies on cerebrovascular alterations in metabolic syndrome and their associations with neurodegenerative disease models in medaka.

Protective effect of neuropeptide Y2 receptor activation against methamphetamine-induced brain endothelial cell alterations

Methamphetamine (METH) consumption is a health problem that leads to neurological and psychiatric disturbances. The cellular alterations behind these conditions have been extensively investigated and it is now well-established that METH causes cerebrovascular alterations being a key feature in drug-induced neuropathology.Although promising advances in understanding the blood-brain barrier (BBB) alterations induced by METH, there is still no available approach to counteract or diminish such effects. Interestingly, several studies show that neuropeptide Y (NPY) has an important protective role against METH-induced neuronal and glial toxicity, as well as behavioral deficits. Despite these beneficial effects of the NPY system, nothing is known about its role in brain endothelial cells under conditions of METH exposure.Thus, our aim was to unravel the effect of NPY and its receptors against METH-induced endothelial cell dysfunction. For that, we used a human brain microvascular endothelial cell line (hCMEC/D3) and our results demonstrate that endothelial cells express both NPY Y1 (Y1R) and Y2 (Y2R) receptors, but only Y2R is upregulated after METH exposure. Moreover, this drug of abuse induced endothelial cell death and elicited the production of reactive oxygen species (ROS) by these cells, which were prevented by the activation of Y2R. Additional, cell death and oxidative stress triggered by METH were dependent on the concentration of the drug. In sum, with the present study we identified for the first time the NPY system, and particularly the Y2R subtype, as a promising target to protect against METH-induced neurovascular dysfunction.

Depression and Cognitive Impairment-Extrahepatic Manifestations of NAFLD and NASH.

Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets.

Pericytes in Neurometabolic Diseases

Since brain pericytes guarantee appropriate development and maintenance of the cerebrovascular system, we reviewed their role in neurometabolic diseases (NMDs), a subclass of inborn errors of metabolism that selectively cause neurological sequels and widespread cerebrovascular alterations. Main findings about pericyte involvement in NMDs arise from glutaric acidemia type I (GA-I) models. In this regard, we found that (i) a single intracisternal injection of the main accumulated metabolite (glutaric acid, GA) in rat neonates disturbed the neurovascular unit (NVU) as evidenced by blood-brain barrier hyperpermeability, and altered immunoreactivity of pericyte and astrocyte markers surrounding brain microvessels; (ii) GA-elicited capillary constriction near pericyte somata likely inducing reduced brain blood flow as reported in GA-I patients; (iii) GA-elicited pericyte contraction probably results from a defective interplay among NVU components and could be relevant in case of metabolic decompensation or energetic deficiency. Although pericyte pathological features have been studied in few NMDs, their involvement in NMD pathophysiology is largely unknown. Thus, further studies are needed to identify their roles and therapeutic potentiality.

The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia.

Executive dysfunction is a predominant cognitive symptom in cerebral small vessel disease (SVD). The Institute of Cognitive Neurology Frontal Screening (IFS) is a well-validated screening tool allowing the rapid assessment of multiple components of executive function in Spanish-speaking individuals. In this study, we examined performance on the IFS in subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited condition leading to the early onset of SVD. We further explored associations between performance on the IFS and magnetic resonance imaging (MRI) markers of SVD. We recruited 24 asymptomatic CADASIL subjects and 23 noncarriers from Colombia. All subjects underwent a research MRI and a neuropsychological evaluation, including the IFS. Structural MRI markers of SVD were quantified in each subject, together with an SVD Sum Score representing the overall burden of cerebrovascular alterations. General linear model, correlation, and receiver operating characteristic curve analyses were used to explore group differences on the IFS and relationships with MRI markers of SVD. CADASIL subjects had a significantly reduced performance on the IFS Total Score. Performance on the IFS correlated with all quantified markers of SVD, except for brain atrophy and perivascular spaces enlargement. Finally, while the IFS Total Score was not able to accurately discriminate between carriers and noncarriers, it showed adequate sensitivity and specificity in detecting the presence of multiple MRI markers of SVD. These results suggest that the IFS may be a useful screening tool to assess executive function and disease severity in the context of SVD.

Acute Dilation of Venous Sinuses in Animal Models of Mild Traumatic Brain Injury Detected Using 9.4T MRI.

Mild traumatic brain injury (mTBI) is a debilitating but extremely common form of brain injury that affects a substantial number of people each year. mTBI is especially common in children and adolescents. Our understanding of mTBI pathophysiology is limited, and there is currently no accepted marker for disease severity. A potential marker for disease severity may be cerebrovascular dysfunction. Recent findings have implicated cerebrovascular alteration as an important component of mTBI and suggest it contributes to the development of persistent, long-term symptoms. In this paper, we conducted two studies to investigate whether mTBI affects venous drainage patterns in the central nervous system using alterations in the size of venous sinuses as a marker of changes in drainage. Using a closed head vertical weight-drop model and a lateral impact injury model of mTBI, we imaged and quantified the size of three major draining vessels in the adolescent rat brain using 9.4T MRI. Areas and volumes were quantified in the superior sagittal sinus and left and right transverse sinuses using images acquired from T2w MRI in one study and post-gadolinium T1w MRI in another. Our results indicated that the three venous sinuses were significantly larger in mTBI rats as compared to sham rats 1-day post injury but recovered to normal size 2 weeks after. Acutely enlarged sinuses post-mTBI may indicate abnormal venous drainage, and this could be suggestive of a cerebrovascular response to trauma.

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.

Brain-Immune Interactions and Neuroinflammation After Traumatic Brain Injury.

Traumatic brain injury (TBI) is the principal cause of death and disability in children and young adults. Clinical and preclinical research efforts have been carried out to understand the acute, life-threatening pathophysiological events happening after TBI. In the past few years, however, it was recognized that TBI causes significant morbidity weeks, months, or years after the initial injury, thereby contributing substantially to the overall burden of TBI and the decrease of life expectancy in these patients. Long-lasting sequels of TBI include cognitive decline/dementia, sensory-motor dysfunction, and psychiatric disorders, and most important for patients is the need for socio-economic rehabilitation affecting their quality of life. Cerebrovascular alterations have been described during the first week after TBI for direct consequence development of neuroinflammatory process in relation to brain edema. Within the brain–immune interactions, the complement system, which is a family of blood and cell surface proteins, participates in the pathophysiology process. In fact, the complement system is part of the primary defense and clearance component of innate and adaptive immune response. In this review, the complement activation after TBI will be described in relation to the activation of the microglia and astrocytes as well as the blood–brain barrier dysfunction during the first week after the injury. Considering the neuroinflammatory activity as a causal element of neurological handicaps, some major parallel lines of complement activity in multiple sclerosis and Alzheimer pathologies with regard to cognitive impairment will be discussed for chronic TBI. A better understanding of the role of complement activation could facilitate the development of new therapeutic approaches for TBI.

Brain involvement in non-alcoholic fatty liver disease (NAFLD): A systematic review

Non-alcoholic fatty liver disease (NAFLD) is associated with high cardiovascular morbidity and mortality which usually is considered to be related to cardiac involvement, while scarce attention is addressed to brain damage. Viceversa NAFLD is associated with asymptomatic brain lesions, alterations in cerebral perfusion and activity, cognitive impairment and brain aging and with increased risk and severity of both ischemic and haemorrhagic stroke. Besides known metabolic risk factors, NAFLD is characterized by a pro inflammatory state, which contributes to atherosclerosis and microglia activation, endothelial dysfunction, pro-coagulant state and platelets activation, which in turn promote both micro and macrovascular damage eventually responsible for clinical and subclinical cerebrovascular alterations. A better knowledge of the association between NAFLD and brain alterations could lead to an improved management of risk factors underpinning both liver and cerebral disease, possibly preventing the progression of asymptomatic brain lesions to clinical cerebrovascular accidents.