Exploratory Translational Modeling Approach in Drug Development to Predict Human Brain Pharmacokinetics and Pharmacologically Relevant Clinical Doses

2012 ◽  
Vol 40 (5) ◽  
pp. 877-883 ◽  
Author(s):  
W. Kielbasa ◽  
R. E. Stratford
Keyword(s):  
Drug Development ◽  
Human Brain ◽  
Modeling Approach ◽  
Translational Modeling

Age Effect in Human Brain Responses to Emotion Arousing Images: The EEG 3D-Vector Field Tomography Modeling Approach

2015 ◽  
Vol 7 (3) ◽  
pp. 223-235 ◽  
Author(s):  
Chrysa D. Papadaniil ◽  
Vasiliki E. Kosmidou ◽  
Anthoula C. Tsolaki ◽  
Leontios J. Hadjileontiadis ◽  
Magda Tsolaki ◽  
...  
Keyword(s):  
Vector Field ◽  
Human Brain ◽  
Age Effect ◽  
Modeling Approach ◽  
Brain Responses

scholarly journals Combining PET Biodistribution and Equilibrium Dialysis Assays to Assess the Free Brain Concentration and BBB Transport of CNS Drugs

2012 ◽  
Vol 32 (5) ◽  
pp. 874-883 ◽  
Author(s):  
Roger N Gunn ◽  
Scott G Summerfield ◽  
Cristian A Salinas ◽  
Kevin D Read ◽  
Qi Guo ◽  
...  
Keyword(s):  
Drug Development ◽  
Human Brain ◽  
Concentration Gradient ◽  
Equilibrium Dialysis ◽  
Active Efflux ◽  
Brain Concentration ◽  
Drug Candidates ◽  
Positron Emission

The passage of drugs in and out of the brain is controlled by the blood—brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development.

Language processing is not a race against time

2016 ◽  
Vol 39 ◽  
Author(s):  
Giosuè Baggio ◽  
Carmelo M. Vicario
Keyword(s):  
Information Processing ◽  
Human Brain ◽  
Language Processing ◽  
Cognitive Functions ◽  
Memory Systems ◽  
Language System ◽  
Moderating Factors

AbstractWe agree with Christiansen & Chater (C&C) that language processing and acquisition are tightly constrained by the limits of sensory and memory systems. However, the human brain supports a range of cognitive functions that mitigate the effects of information processing bottlenecks. The language system is partly organised around these moderating factors, not just around restrictions on storage and computation.

Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

1985 ◽  
Vol 43 ◽  
pp. 726-729
Author(s):  
K.S. Kosik ◽  
L.K. Duffy ◽  
S. Bakalis ◽  
C. Abraham ◽  
D.J. Selkoe
Keyword(s):  
Monoclonal Antibodies ◽  
Alzheimer Disease ◽  
Human Brain ◽  
Neurofibrillary Tangles ◽  
Morphological Analysis ◽  
High Specificity ◽  
Cytoskeletal Proteins ◽  
Neuritic Plaque ◽  
Protein Chemistry ◽  
Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

Toward a neuroscope: An application of high-performance computing for real-time evaluation of brain function using MRI

1994 ◽  
Vol 52 ◽  
pp. 922-923
Author(s):  
C. S. Potter ◽  
C. D. Gregory ◽  
H. D. Morris ◽  
Z.-P. Liang ◽  
P. C. Lauterbur
Keyword(s):  
Human Brain ◽  
Brain Function ◽  
High Performance ◽  
Complex Signal ◽  
Time Step ◽  
Brain Organization ◽  
Cognitive Studies ◽  
Positron Emission ◽  
Imaging And Spectroscopy ◽  
3D Anatomy

Over the past few years, several laboratories have demonstrated that changes in local neuronal activity associated with human brain function can be detected by magnetic resonance imaging and spectroscopy. Using these methods, the effects of sensory and motor stimulation have been observed and cognitive studies have begun. These new methods promise to make possible even more rapid and extensive studies of brain organization and responses than those now in use, such as positron emission tomography.Human brain studies are enormously complex. Signal changes on the order of a few percent must be detected against the background of the complex 3D anatomy of the human brain. Today, most functional MR experiments are performed using several 2D slice images acquired at each time step or stimulation condition of the experimental protocol. It is generally believed that true 3D experiments must be performed for many cognitive experiments. To provide adequate resolution, this requires that data must be acquired faster and/or more efficiently to support 3D functional analysis.

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