Central Nervous System (CNS) and Blood-Brain Barrier (BBB)
Blood-Brain Barrier (BBB) is a distinctive and tightly regulated interface between the central nervous system (CNS) and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. The barrier functions are dynamic and respond to regulatory signals from both blood and brain. BBB and the blood- cerebrospinal fluid (CSF)-barrier (BCSFB) govern drug transfer into and out of the brain. The BBB consists of cerebrovascular endothelial cells while the BCSFB consists of choroid plexus (CP) epithelial cells. Together with the BBB and BCSFB transport characteristics and surface areas, the drug characteristics (lipophilicity, size, shape, charge, affinity for a transporter, etc.) determine the actual transport rate and extent.
Creative Biolabs provides a series of technologies to analyze the transport of the CNS from the perspective of physiology/pharmacology, which provides the most credible information for your next research about psychotropic drug development.
In Vivo Techniques in the Study of CNS Transport
Several in vivo techniques have been developed by Creative Biolabs to study and measure the uptake of CNS compounds into the brain.
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Intravenous Injection/ Brain Sampling
Advantages: Most physiological approach; highest sensitivity; low technical difficulty.
Disadvantages/ Caveats: May require good analytical tools to exclude metabolite uptake and careful pharmacokinetic analysis to discriminate unidirectional uptake versus bidirectional transfer.
Advantages: Fast procedure; moderate technical difficulty; permits a wide range of modifications of injectate composition; artifacts by metabolism largely excluded.
Disadvantages/ Caveats: Relatively insensitive (compared with intravenous injection and brain perfusion).
Advantages: Higher sensitivity compared with BUI; permits modification of both perfusate composition and flow rates; artifacts by peripheral metabolism excluded.
Disadvantages/ Caveats: Technically more difficult than intravenous experiments and BUI.
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Quantitative Autoradiography
Advantages: Excellent spatial resolution.
Disadvantages/ Caveats: Time-consuming evaluation; no proof of the integrity of tracer.
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External Registration: Magnetic Resonance Imaging (MRI), Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET)
Advantages: Noninvasive and applicable in humans; allow time course measurements in individual subjects.
Disadvantages/ Caveats: Expensive equipment (MRI, PET) and tracers (PET); limited sensitivity (MRI) and availability of labeled tracers (MRI, PET); poor spatial resolution for small animals (SPECT).
Advantages: Allows time course measurements in individual subjects; samples well suited for subsequent analytical procedures.
Disadvantages/ Caveats: Technically involved; in vivo probe calibration required for valid quantitative evaluation; local damage to BBB integrity.
Advantages: Readily accessible for sampling; applicable to humans.
Disadvantages/ Caveats: Reflects permeability of BCSFB and CSF fluid dynamics rather than BBB.
In Vitro Techniques in the Study of CNS
Several in vitro techniques also can measure the uptake of CNS compounds into the brain.
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Fresh Isolated Brain Microvessels
Advantages: Representing the in vivo expression of transporters and efflux systems at the BBB.
Disadvantages/ Caveats: Transcellular passage cannot be measured.
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Primary Cultures, Cell Lines
Advantages: Permeability screening experiments (feasible with primary endothelial cell (EC) from bovine/porcine sources); effect of culture conditions on BBB transport properties may be studied (astroglial factors, serum effects, inflammatory stimuli, hypoxia/aglycemia).
Disadvantages/ Caveats: No system yet able to represent in vivo condition for barrier tightness and BBB specific transporter expression; the multitude of models makes the comparison of results between studies difficult.
As a leader in the field of psychotropic drug research, Creative Biolabs has the responsibility and obligation to help every researcher solve the technical problems. If you have any questions, please contact us.
For Research Use Only.
