Blood Brain Barrier
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2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hui Li ◽  
Guochao Han ◽  
Dongruo He ◽  
Ying Wang ◽  
Yuan Lin ◽  
...  

This study aimed to explore the expression level of miR-539 in the blood-brain barrier permeability induced by cerebrovascular occlusion and its mediated mechanism. Altogether, 48 patients with cerebral vascular occlusion lesions from March 2018 to June 2020 were collected. The expression level of miR-539 in the peripheral blood serum of the subjects was analyzed by qRT-PCR, and the participants were divided into two groups according to the results of head and neck ultrasound and CTA hemodynamics. The MCAO model of cerebral ischemia was established in rats, and the expression level of miR-539 was detected by qRT-PCR in brain tissues of different groups of rats. The effects of miR-539 on the permeability of blood-brain barrier were investigated by intraventricular injection of agomiR-539 and antagomir-539. The model of blood-brain barrier was established by culturing brain microvascular endothelial cells and pericytes in vitro, and the changes of miR-539 expression level and permeability after glucose and oxygen deprivation were detected. The expression level of SNAI2/MMP9 signaling pathway protein in cells was detected by Western blot. Compared with the healthy control group, the expression level of miR-539 in peripheral blood of patients with cerebrovascular occlusive disease decreased significantly, and the expression level of miR-539 in the MCAO rat model decreased and affected the permeability of blood-brain barrier. Glucose and oxygen deprivation treatment in brain microvascular endothelial cells can lead to downregulation of miR-539 expression and affect cell permeability. miR-539 in brain microvascular endothelial cells can target and bind to SNAI2 and participate in the regulation of endothelial cell permeability by affecting the SNAI2/MMP9 signaling pathway. The results of this study suggested that circulating miR-539 in peripheral blood may be a potential marker for predicting blood-brain barrier permeability after ischemic stroke. More detailed studies are needed to determine its diagnostic value.


2021 ◽  
Author(s):  
Rory K.M. Long ◽  
Livia Piatti ◽  
François Korbmacher ◽  
Maria Bernabeu

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lesley Hoyles ◽  
Matthew G. Pontifex ◽  
Ildefonso Rodriguez-Ramiro ◽  
M. Areeb Anis-Alavi ◽  
Khadija S. Jelane ◽  
...  

Abstract Background Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and l-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. Results Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. Conclusion Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.


2021 ◽  
Author(s):  
Angelika Hoffmann ◽  
Jessica Jin ◽  
Mame Aida ◽  
Chi Ho Wai ◽  
Sanjib Mohanty ◽  
...  

Brain swelling occurs in cerebral malaria (CM) and may either reverse or result in fatal outcome. It is currently unknown how brain swelling in CM reverses, as investigations have been hampered by inadequate animal models. In this study, we show that reversible brain swelling in experimental murine cerebral malaria (ECM) can be induced reliably after single vaccination with radiation-attenuated sporozoites as revealed by in vivo high-field (9.4T) magnetic resonance imaging. Our results provide evidence that parenchymal fluid increase and consecutive brain swelling results from transcellular blood-brain barrier disruption (BBBD), as revealed by electron microscopy. This mechanism enables reversal of brain swelling but does not prevent persistent focal brain damage, evidenced by microhemorrhages, in areas of most severe BBBD. In a cohort of 27 pediatric and adult CM patients (n=4 fatal, n=23 non-fatal) two out of four fatal CM patients (50%) and 8 out of 23 non-fatal CM patients (35%) showed microhemorrhages on MRI at clinical field strength of 1.5T, emphasizing the translational potential of the experimental model.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Wang ◽  
Zhongguo Song ◽  
Yanning Yuan ◽  
Guozhen Guo ◽  
Jianjun Kang

AbstractThe presence of blood–brain barrier (BBB) is a major obstacle to effectively deliver therapeutics to the central nervous system (CNS); hence, the outcomes following treatment of CNS diseases remain unsatisfactory. Fortunately, electromagnetic pulses (EMPs) provide a non-invasive method to locally open the BBB. To obtain the optimal pulse parameters of EMP-induced BBB opening to ensure the effective delivery of CNS drugs, it is particularly important to measure and assess the effects of pulse parameters on the temperature distribution in the human head exposed to EMPs. In this paper, the specific anthropomorphic mannequin phantom was adopted and the temperature increase in the human head induced by EMPs of different parameters was estimated in the software “COMSOL Multiphysics”. The results show that the temperature distribution profiles with different EMP parameters have almost similar characteristics, the highest temperature increase values in the human head are positively correlated with variations of EMP parameters, and potential hazards to the human head may occur when EMP parameters exceed the safety threshold, which will provide theoretical basis for seeking the optimal EMP parameters to open the BBB to the greatest extent within a safe range.


2021 ◽  
Author(s):  
Fang Zhou ◽  
Pearl Ebea ◽  
Ezra Mutai ◽  
Sonal Sukreet ◽  
Shya Navazesh ◽  
...  

Background: Human milk contains large amounts of exosomes (MEs) and their regulatory microRNA cargos, whereas infant formulas contain only trace amounts of MEs and microRNAs. Breastfeeding has been implicated in optimal brain development but experimental evidence linking ME intake with brain development is limited. Objectives: We assessed the transport of MEs across the blood-brain barrier (BBB) and ME accumulation in distinct regions of the brain in brain endothelial cells and suckling mice. We further assessed BME-dependent gene expression profiles and effects on the dendritic complexity of hippocampal granule cells and phenotypes of BME depletion in neonate, juvenile and adult mice. Methods: The transfer of MEs across the BBB was assessed by using bovine MEs labeled with FM4-64 or loaded with IRDye-labeled miR-34a in murine brain endothelial bEnd.3 cell monolayers and dual chamber systems, and in wild-type newborn pups fostered to exosome and cargo tracking (ECT) dams that express MEs endogenously labeled with a CD63-eGFP fusion protein for subsequent analysis by serial two-photon tomography and staining with anti-eGFP antibodies. Effects of MEs on gene expression and dendritic architecture of granule cells was analyzed in hippocampi from juvenile mice fed exosome and RNA-depleted (ERD) and exosome and RNA-sufficient (ERS) diets by using RNA-sequencing analysis and Golgi-Cox staining followed by integrated neuronal tracing and morphological analysis of neuronal dendrites, respectively. Spatial learning and severity of kainic acid-induced seizures were assessed in mice fed ERD and ERS diets. Results: bEnd.3 cells internalized MEs by using a saturable transport mechanism and secreted miR-34a across the basal membrane. MEs penetrated the entire brain in fostering experiments; major regions of accumulation included the hippocampus, cortex and cerebellum. Two hundred ninety-five genes were differentially expressed in hippocampi from male mice fed ERD and ERS diets; high-confidence gene networks included pathways implicated in axon guidance and calcium signaling. Only one gene was differentially expressed in females fed the experimental diets. Juvenile pups fed the ERD diet had reduced dendritic complexity of dentate granule cells in the hippocampus, scored nine-fold lower in the Barnes maze test of spatial learning and memory (P < 0.01), and the severity of seizures was 5-fold higher following kainic acid administration in adult mice fed the ERD diet compared to mice fed the ERS diet (P < 0.01). Conclusions: MEs cross the BBB and contribute toward optimal neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice.


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