scholarly journals Computer classification models on the relationship between chemical structures of compounds and drugs with their blood brain barrier penetration

2012 ◽  
Vol 58 (3) ◽  
pp. 246-256
Author(s):  
O.A. Raevsky ◽  
S.L. Solodova ◽  
O.E. Raevskaya ◽  
Y.V. Liplavskiy ◽  
R.M. Mannhold
Keyword(s):  
Blood Brain Barrier ◽  
Computer Modelling ◽  
Brain Barrier ◽  
Data Set ◽  
Linear Discriminant ◽  
Chemical Structures ◽  
Blood Brain ◽  
Donor Acceptor ◽  
The Central Nervous System ◽  
The Relationship

Ability of drugs to cross blood-brain barrier (BBB) (BBB+ for BBB-penetrating and BBB- for non-penetrating compounds) is one of the most important properties of chemicals acting on the central nervous system (CNS). This work presents the results of modelling of the relationship between chemicals structure and BBB-crossing ability. The data set included 1513 compounds BBB+/- (1276 BBB+ and 237 BBB-). Computer modelling of structure-activity relationship was realized by two directions: using the "read-across" method and linear discriminant analysis (LDA) based on physico-chemical descriptors. It was found that a sum of donor-acceptor factors is the principal parameter, which define BBB penetration.

scholarly journals Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyao Peng ◽  
Zhixuan Luo ◽  
Shuang He ◽  
Luhua Zhang ◽  
Ying Li
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Function ◽  
Vascular System ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
The Relationship

As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.

scholarly journals Senescence and associated blood–brain barrier alterations in vitro

2021 ◽  
Author(s):  
Ellaine Salvador ◽  
Malgorzata Burek ◽  
Mario Löhr ◽  
Michiaki Nagai ◽  
Carsten Hagemann ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Intercellular Junctions ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Initial Attempt ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Vitro Model ◽  
The Relationship

AbstractProgressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood–brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.

scholarly journals Blood‒Brain Barrier Pathology and CNS Outcomes in Streptococcus pneumoniae Meningitis

2018 ◽  
Vol 19 (11) ◽  
pp. 3555 ◽  
Author(s):  
Belinda Yau ◽  
Nicholas Hunt ◽  
Andrew Mitchell ◽  
Lay Too
Keyword(s):  
Streptococcus Pneumoniae ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Early Step ◽  
Neurological Sequelae ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Relationship ◽  
Host Inflammatory Response

Streptococcus pneumoniae is a major meningitis-causing pathogen globally, bringing about significant morbidity and mortality, as well as long-term neurological sequelae in almost half of the survivors. Subsequent to nasopharyngeal colonisation and systemic invasion, translocation across the blood‒brain barrier (BBB) by S. pneumoniae is a crucial early step in the pathogenesis of meningitis. The BBB, which normally protects the central nervous system (CNS) from deleterious molecules within the circulation, becomes dysfunctional in S. pneumoniae invasion due to the effects of pneumococcal toxins and a heightened host inflammatory environment of cytokines, chemokines and reactive oxygen species intracranially. The bacteria‒host interplay within the CNS likely determines not only the degree of BBB pathological changes, but also host survival and the extent of neurological damage. This review explores the relationship between S. pneumoniae bacteria and the host inflammatory response, with an emphasis on the BBB and its roles in CNS protection, as well as both the acute and long-term pathogenesis of meningitis.

scholarly journals Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarinnapha M. Vasunilashorn ◽  
◽  
Long H. Ngo ◽  
Simon T. Dillon ◽  
Tamara G. Fong ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Brain Barrier ◽  
Markers Of Inflammation ◽  
Blood Brain ◽  
Csf Levels ◽  
The Relationship

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

scholarly journals Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

2021 ◽  
Vol 22 (7) ◽  
pp. 3356
Author(s):  
Manon Leclerc ◽  
Stéphanie Dudonné ◽  
Frédéric Calon
Keyword(s):  
Natural Products ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Omega 3 ◽  
Indirect Pathway ◽  
Brain Functions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Peripheral Metabolism

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.

scholarly journals Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

2019 ◽  
Vol 20 (3) ◽  
pp. 571 ◽  
Author(s):  
Shotaro Michinaga ◽  
Yutaka Koyama
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secondary Damage ◽  
The Central Nervous System ◽  
Bbb Permeability ◽  
Novel Therapeutic Strategies ◽  
Glial Derived Neurotrophic Factor ◽  
Endothelial Growth Factors

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

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