scholarly journals Effects of Neonatal Systemic Inflammation on Blood-Brain Barrier Permeability and Behaviour in Juvenile and Adult Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
H. B. Stolp ◽  
P. A. Johansson ◽  
M. D. Habgood ◽  
K. M. Dziegielewska ◽  
N. R. Saunders ◽  
...  

Several neurological disorders have been linked to inflammatory insults suffered during development. We investigated the effects of neonatal systemic inflammation, induced by LPS injections, on blood-brain barrier permeability, endothelial tight junctions and behaviour of juvenile (P20) and adult rats. LPS-treatment resulted in altered cellular localisation of claudin-5 and changes in ultrastructural morphology of a few cerebral blood vessels. Barrier permeability to sucrose was significantly increased in LPS treated animals when adult but not at P20 or earlier. Behavioural tests showed that LPS treated animals at P20 exhibited altered behaviour using prepulse inhibition (PPI) analysis, whereas adults demonstrated altered behaviour in the dark/light test. These data indicate that an inflammatory insult during brain development can change blood-brain barrier permeability and behaviour in later life. It also suggests that the impact of inflammation can occur in several phases (short- and long-term) and that each phase might lead to different behavioural modifications.

10.12737/2743 ◽  
2013 ◽  
Vol 20 (4) ◽  
pp. 113-115
Author(s):  
Соколов ◽  
D. Sokolov ◽  
Ильичева ◽  
V. Ilicheva ◽  
Минасян ◽  
...  

The purpose of the study is to estimate the permeability of haemocapillaries in archicortex and paleocortex at alcohol intoxication and under the influence of ionizing irradiation. The experiment was carried out on 168 mature white inbred male rats of 180-200 g by mass at the age of 2.5-3 months, which were divided into 4 groups. In the first group of animals were irradiated by g-quanta 60Co dose of 87.5 Grams; run the second group of animals 15% aqueous ethanol solution in the dose of 2.25 g/kg was introduced intraperitoneally; in the third group the radiation monitoring was held; in the fourth group the ethanol control (injection of saline in similar dose) was carried out. The alkaline phosphatase was identified by a-naphthilphosphate and strong blue PP. The results were estimated statistically. The same type of activities changes of the alkaline phosphatase have been determined experimentally in pyri-form cortex and hippocampus at early phases of postradiation period, unlike the same phases of alcohol intoxication. Both of the studied factors provoke an hour after the impact of the development of destructive changes in the structures of the blood-brain barrier. Th determined changes of blood-brain barrier permeability depends on the phylogenetic age of parts of the cortex and manifest more sig nificant in younger formations (hippocampus) than in older ones (pyriform cortex).


2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.


Sign in / Sign up

Export Citation Format

Share Document