Maternal n-3 enriched diet reprograms the offspring neurovascular transcriptome and blunts inflammation induced by endotoxin in the neonate.

Infection during the perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) transforms brain lipid composition in the offspring and protects the neonatal brain from stroke, in part by blunting injurious immune responses. Critical to the interface between the brain and systemic circulation is the vasculature, endothelial cells in particular, that support brain homeostasis and provide a barrier to systemic infection.

Musculoskeletal perturbations of deep space radiation: Assessment using a Gateway MRI.

Human space exploration expansion from Low-Earth Orbit to deep space is accelerating the need to monitor and address the known health concerns related to deep space radiation. The human musculoskeletal system is vulnerable to these risks (alongside microgravity) and its health reflects the well-being of other body systems. Multiparametric magnetic resonance imaging (MRI) is an important approach for assessing temporal physiological changes in the musculoskeletal system.

Maternal n-3 enriched diet reprograms neurovascular transcriptome and blunts inflammation in neonate.

Infection during perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (PUFA) transforms brain lipid composition and protects from neonatal stroke. Vasculature is a critical interface between blood and brain providing a barrier to systemic infection.

Cortical cerebrovascular and metabolic perturbations in the 5xFAD mouse model of Alzheimer's disease.

Introduction: The 5xFAD mouse is a popular model of familial Alzheimer's disease (AD) that is characterized by early beta-amyloid (Aβ) deposition and cognitive decrements. Despite numerous studies, the 5xFAD mouse has not been comprehensively phenotyped for vascular and metabolic perturbations over its lifespan.

Methods: Male and female 5xFAD and wild type (WT) littermates underwent F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging at 4, 6, and 12 months of age to assess regional glucose metabolism.

Seeking the Amygdala: Novel Use of Diffusion Tensor Imaging to Delineate the Basolateral Amygdala.

The amygdaloid complex, including the basolateral nucleus (BLA), contributes crucially to emotional and cognitive brain functions, and is a major target of research in both humans and rodents. However, delineating structural amygdala plasticity in both normal and disease-related contexts using neuroimaging has been hampered by the difficulty of unequivocally identifying the boundaries of the BLA. This challenge is a result of the poor contrast between BLA and the surrounding gray matter, including other amygdala nuclei.

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer's Disease.

Vascular dysfunction and structural abnormalities in Alzheimer's disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels and the cortical vascular network across the lifespan. Our vessel painting approach was used to label the entire cortical vasculature, followed by epifluorescence microscopy.

Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus.

Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE.

Longitudinal dynamics of microvascular recovery after acquired cortical injury.

Acquired brain injuries due to trauma damage the cortical vasculature, which in turn impairs blood flow to injured tissues. There are reports of vascular morphological recovery following traumatic brain injury, but the remodeling process has not been examined longitudinally in detail after injury in vivo. Understanding the dynamic processes that influence recovery is thus critically important.

Neuroimaging of Mouse Models of Alzheimer's Disease.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) have made great strides in the diagnosis and our understanding of Alzheimer's Disease (AD). Despite the knowledge gained from human studies, mouse models have and continue to play an important role in deciphering the cellular and molecular evolution of AD. MRI and PET are now being increasingly used to investigate neuroimaging features in mouse models and provide the basis for rapid translation to the clinical setting.

NAAA-regulated lipid signaling governs the transition from acute to chronic pain.

Chronic pain affects 1.5 billion people worldwide but remains woefully undertreated. Understanding the molecular events leading to its emergence is necessary to discover disease-modifying therapies.

Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis.

Stroke is among the top ten causes of death in children but has received disproportionally little attention. Cerebral arteriopathies account for up to 80% of childhood arterial ischemic stroke (CAIS) cases and are strongly predictive of CAIS recurrence and poorer outcomes. The underlying mechanisms of sensitization of neurovasculature by viral infection are undefined.

Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms.

The present study explored the hypothesis that an adverse intrauterine environment caused by maternal undernutrition (MUN) acted through corticosteroid-dependent and -independent mechanisms to program lasting functional changes in the neonatal cerebrovasculature and vulnerability to mild hypoxic-ischemic (HI) injury. From day 10 of gestation until term, MUN and MUN-metyrapone (MUN-MET) group rats consumed a diet restricted to 50% of calories consumed by a pair-fed control; and on gestational day 11 through term, MUN-MET groups received drinking water containing MET (0.5 mg/mL), a corticosteroid synthesis inhibitor.

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials.

The DNA vaccine, AV-1959D, targeting N-terminal epitope of Aβ peptide, has been proven immunogenic in mice, rabbits, and non-human primates, while its therapeutic efficacy has been shown in mouse models of Alzheimer's disease (AD). Here we report for the first time on IND-enabling biodistribution and safety/toxicology studies of cGMP-grade AV-1959D vaccine in the Tg2576 mouse model of AD. We also tested acute neuropathology safety profiles of AV-1959D in another AD disease model, Tg-SwDI mice with established vascular and parenchymal Aβ pathology in a pre-clinical translational study.

Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics.

Intranasal recombinant osteopontin (OPN) has been shown to be neuroprotective in different models of acquired brain injury but has never been tested after traumatic brain injury (TBI). We used a model of moderate-to-severe controlled cortical impact in male adult Sprague Dawley rats and tested our hypothesis that OPN treatment would improve neurological outcomes, lesion and brain tissue characteristics, neuroinflammation, and vascular characteristics at 1 day post-injury. Intranasal OPN administered 1 hr after the TBI did not improve neurological score, lesion volumes, blood-brain barrier, or vascular characteristics.

CX3CR1-CCR2-dependent monocyte-microglial signaling modulates neurovascular leakage and acute injury in a mouse model of childhood stroke.

Stroke is among the top 10 causes of death in children. The developmental stage of the brain is central to stroke pathophysiology. The incidence of childhood arterial ischemic stroke (CAIS) is lower than of perinatal arterial ischemic stroke but the rate of recurrence is strikingly high.

A Novel Technique for Visualizing and Analyzing the Cerebral Vasculature in Rodents.

We introduce a novel protocol to stain, visualize, and analyze blood vessels from the rat and mouse cerebrum. This technique utilizes the fluorescent dye, DiI, to label the lumen of the vasculature followed by perfusion fixation. Following brain extraction, the labeled vasculature is then imaged using wide-field fluorescence microscopy for axial and coronal images and can be followed by regional confocal microscopy.

Male and Female Mice Exhibit Divergent Responses of the Cortical Vasculature to Traumatic Brain Injury.

We previously reported that traumatic brain injuries (TBI) alter the cerebrovasculature near the injury site in rats, followed by revascularization over a 2-week period. Here, we tested our hypothesis that male and female adult mice have differential cerebrovascular responses following a moderate controlled cortical impact (CCI). Using in vivo magnetic resonance imaging (MRI), a new technique called vessel painting, and immunohistochemistry, we found no differences between males and females in lesion volume, neurodegeneration, blood-brain barrier (BBB) alteration, and microglia activation.

Modulating the water channel AQP4 alters miRNA expression, astrocyte connectivity and water diffusion in the rodent brain.

Aquaporins (AQPs) facilitate water diffusion through the plasma membrane. Brain aquaporin-4 (AQP4) is present in astrocytes and has critical roles in normal and disease physiology. We previously showed that a 24.

Up-regulation of Wnt/β-catenin expression is accompanied with vascular repair after traumatic brain injury.

Recent data suggest that repairing the cerebral vasculature after traumatic brain injury (TBI) may help to improve functional recovery. The Wnt/β-catenin signaling pathway promotes blood vessel formation during vascular development, but its role in vascular repair after TBI remains elusive. In this study, we examined how the cerebral vasculature responds to TBI and the role of Wnt/β-catenin signaling in vascular repair.

Chronic cerebrovascular dysfunction after traumatic brain injury.

Traumatic brain injuries (TBI) often involve vascular dysfunction that leads to long-term alterations in physiological and cognitive functions of the brain. Indeed, all the cells that form blood vessels and that are involved in maintaining their proper function can be altered by TBI. This Review focuses on the different types of cerebrovascular dysfunction that occur after TBI, including cerebral blood flow alterations, autoregulation impairments, subarachnoid hemorrhage, vasospasms, blood-brain barrier disruption, and edema formation.

NURR1 involvement in recombinant tissue-type plasminogen activator treatment complications after ischemic stroke.

Background And Purpose: Despite the effectiveness of recombinant tissue-type plasminogen activator (r-tPA) during the acute phase of ischemic stroke, the therapy remains limited by a narrow time window and the occurrence of occasional vascular side effects, particularly symptomatic hemorrhages. Our aim was to investigate the mechanisms underlying the endothelial damage resulting from r-tPA treatment in ischemic-like conditions.

Methods: Microarray analyses were performed on cerebral endothelial cells submitted to r-tPA treatment during oxygen and glucose deprivation to identify novel biomarker candidates.

Juvenile traumatic brain injury induces long-term perivascular matrix changes alongside amyloid-beta accumulation.

In our juvenile traumatic brain injury (jTBI) model, emergence of cognitive dysfunctions was observed up to 6 months after trauma. Here we hypothesize that early brain injury induces changes in the neurovascular unit (NVU) that would be associated with amyloid-beta (Aβ) accumulation. We investigated NVU changes for up to 6 months in a rat jTBI model, with a focus on the efflux protein P-glycoprotein (P-gp) and on the basement membrane proteins perlecan and fibronectin, all known to be involved in Aβ clearance.

Aquaporin and brain diseases.

Background: The presence of water channel proteins, aquaporins (AQPs), in the brain led to intense research in understanding the underlying roles of each of them under normal conditions and pathological conditions.

Scope Of Review: In this review, we summarize some of the recent knowledge on the 3 main AQPs (AQP1, AQP4 and AQP9), with a special focus on AQP4, the most abundant AQP in the central nervous system.

Major Conclusions: AQP4 was most studied in several brain pathological conditions ranging from acute brain injuries (stroke, traumatic brain injury) to the chronic brain disease with autoimmune neurodegenerative diseases.

Molecular contributions to neurovascular unit dysfunctions after brain injuries: lessons for target-specific drug development.

The revised 'expanded' neurovascular unit (eNVU) is a physiological and functional unit encompassing endothelial cells, pericytes, smooth muscle cells, astrocytes and neurons. Ischemic stroke and traumatic brain injury are acute brain injuries directly affecting the eNVU with secondary damage, such as blood-brain barrier (BBB) disruption, edema formation and hypoperfusion. BBB dysfunctions are observed at an early postinjury time point, and are associated with eNVU activation of proteases, such as tissue plasminogen activator and matrix metalloproteinases.