Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

Abstract

Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets

“…S7A ). Histamine is considered to poorly penetrate blood–brain barrier (BBB) 39 , but the pineal gland is not covered with the BBB and is one of the communication points between the blood and the brain parenchyma 40 . Based on the above, the highly elevated histamine level in the pineal gland was primarily owing to permeation of the elevated peripheral histamine.…”

Toxicologic Neuropathology of Novel Biotherapeutics

“…The target epitope for these molecules must not compete with or inhibit transferrin binding. One region of the molecule (e.g., the Fc or Fab [“fragment, antigen-binding”] domain) binds TfR1, while another region may bind a target receptor (e.g., TREM2 [triggering receptor expressed on myeloid cells] 156 ) or carry a therapeutic protein (e.g., a recombinant human enzyme 9 ). Within the general framework of the immunoglobulin amino acid sequence (commonly human-derived IgG1), the TfR1 binding domain can be attached to an antibody via a linker, 48 located in one or both Fab regions, 160 or can be provided as a moiety embedded within the Fc domain.…”

Sensoriamento óptico do anticorpo AQP4-IgG utilizando nanobiossensores de nanopartículas de prata associados com epítopos da proteína AQP4

“…Fonte: Traduzido e adaptado de Verheggen et al (2020) Algumas regiões da medula espinhal e dos nervos ópticos apresentam-se mais vulneráveis, já que não têm a BHE completamente desenvolvida, o que permite o acesso do AQP4-IgG periférico. A área postrema é uma região que apresenta um endotélio fenestrado, ou seja, uma BHE incompleta, sendo assim investigada como uma possível via de entrada dos autoanticorpos (Wingerchuk et al 2007;Matiello et al 2013).…”