scholarly journals Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection

2006 ◽  
Vol 74 (12) ◽  
pp. 6982-6991 ◽  
Author(s):  
Peter Bergman ◽  
Linda Johansson ◽  
Hong Wan ◽  
Allison Jones ◽  
Richard L. Gallo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Meningococcal Infection ◽  
Blood Brain ◽  
Bactericidal Properties ◽  
Living Species ◽  
The Brain

ABSTRACT Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.

scholarly journals Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 399 ◽  
Author(s):  
Catarina Chaves ◽  
Xavier Declèves ◽  
Meryam Taghi ◽  
Marie-Claude Menet ◽  
Joelle Lacombe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Pontine Glioma ◽  
Anticancer Drug Delivery ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed (1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14C]-sucrose as measures of BBB integrity, and (2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3H]-SN-38. The unaffected [14C]-sucrose or TRD distribution in the cerebrum, cerebellum, and brainstem regions in DIPG-bearing animals suggests an intact BBB. Targeted proteomics retrieved no change in P-glycoprotein (P-gp), BCRP, MRP1, and MRP4 levels in the analyzed regions of DIPG rats. In vitro, DIPG cells express BCRP but not P-gp, MRP1, or MRP4. Dual inhibition of P-gp/Bcrp, or Mrp showed a significant increase on SN-38 BBB transport: Cerebrum (8.3-fold and 3-fold, respectively), cerebellum (4.2-fold and 2.8-fold), and brainstem (2.6-fold and 2.2-fold). Elacridar increased [3H]-SN-38 brain delivery beyond a P-gp/Bcrp inhibitor effect alone, emphasizing the role of another unidentified transporter in BBB efflux of SN-38. These results confirm a well-preserved BBB in DIPG-bearing rats, along with functional ABC-transporter expression. The development of chemotherapeutic strategies to circumvent ABC-mediated BBB efflux are needed to improve anticancer drug delivery against DIPG.

scholarly journals Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions

2019 ◽  
Vol 20 (7) ◽  
pp. 1632 ◽  
Author(s):  
Michelle Erickson ◽  
William Banks
Keyword(s):  
Central Nervous System ◽  
Immune System ◽  
Blood Brain Barrier ◽  
Neurological Disorders ◽  
Brain Barrier ◽  
Immune Functions ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Age is associated with altered immune functions that may affect the brain. Brain barriers, including the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB), are important interfaces for neuroimmune communication, and are affected by aging. In this review, we explore novel mechanisms by which the aging immune system alters central nervous system functions and neuroimmune responses, with a focus on brain barriers. Specific emphasis will be on recent works that have identified novel mechanisms by which BBB/BCSFB functions change with age, interactions of the BBB with age-associated immune factors, and contributions of the BBB to age-associated neurological disorders. Understanding how age alters BBB functions and responses to pathological insults could provide important insight on the role of the BBB in the progression of cognitive decline and neurodegenerative disease.

scholarly journals The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1237-1249 ◽  
Author(s):  
Ruiqing Kang ◽  
Marcin Gamdzyk ◽  
Cameron Lenahan ◽  
Jiping Tang ◽  
Sheng Tan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Vital Role ◽  
Dual Role ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
M2 Microglia ◽  
The Brain

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

Evaluation of the effect of stress on the blood–brain barrier: critical role of the brain perfusion time

2001 ◽  
Vol 905 (1-2) ◽  
pp. 21-25 ◽  
Author(s):  
Haim Ovadia ◽  
Oded Abramsky ◽  
Shaul Feldman ◽  
Joseph Weidenfeld
Keyword(s):  
Blood Brain Barrier ◽  
Critical Role ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Blood Brain ◽  
Perfusion Time ◽  
The Brain

scholarly journals MicroRNAs in the Blood-Brain Barrier in Hypoxic-Ischemic Brain Injury

2020 ◽  
Vol 18 (12) ◽  
pp. 1180-1186
Author(s):  
Guofang Shen ◽  
Qingyi Ma
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Current Evidence ◽  
Ischemic Brain ◽  
Chronic Disability ◽  
Blood Brain ◽  
Microvascular Response ◽  
The Brain

Hypoxic-ischemic (HI) brain injury is a leading cause of acute mortality and chronic disability in newborns. Current evidence shows that cerebral microvascular response and compromised blood-brain barrier (BBB) integrity occur rapidly and could primarily be responsible for the brain injury observed in many infants with HI brain injury. MicroRNAs (miRNAs) are a type of highly conserved non-coding RNAs (ncRNAs), which consist of 21-25 nucleotides in length and usually lead to suppression of target gene expression. Growing evidence has revealed that brainenriched miRNAs act as versatile regulators of BBB dysfunctions in various neurological disorders including neonatal HI brain injury. In the present review, we summarize the current findings regarding the role of miRNAs in BBB impairment after hypoxia/ischemia brain injury. Specifically, we focus on the recent progress of miRNAs in the pathologies of neonatal HI brain injury. These findings can not only deepen our understanding of the role of miRNAs in BBB impairment in HI brain injury, but also provide insight into the development of new therapeutic strategies for preservation of BBB integrity under pathological conditions.

scholarly journals Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jay P. Patel ◽  
Benicio N. Frey
Keyword(s):  
Bipolar Disorder ◽  
Blood Brain Barrier ◽  
Peripheral Blood ◽  
Critical Role ◽  
Brain Barrier ◽  
Inflammatory Conditions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

The blood-brain barrier (BBB) regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS) in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD), here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species) substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.

scholarly journals Blood–Brain Barrier, Lymphatic Clearance, and Recovery: Ariadne’s Thread in Labyrinths of Hypotheses

2018 ◽  
Vol 19 (12) ◽  
pp. 3818 ◽  
Author(s):  
Oxana Semyachkina-Glushkovskaya ◽  
Dmitry Postnov ◽  
Jürgen Kurths
Keyword(s):  
Blood Brain Barrier ◽  
Lymphatic System ◽  
Metabolic Diseases ◽  
Brain Barrier ◽  
Waste Products ◽  
Brain Functions ◽  
Blood Brain ◽  
New Vision ◽  
The Brain

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria, and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the cerebral lymphatic functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in brain drainage, clearance, and recovery is still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on the connective bridge between the opening of a blood–brain barrier and activation of the meningeal lymphatic clearance. The ability to stimulate the lymph flow in the brain, is likely to play an important role in developing future innovative strategies in neurorehabilitation therapy.

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