Blood-brain barrier transcytosis

Duffy KR, Pardridge WM (1987) Blood-brain barrier transcytosis of insulin in developing rabbits. Brain Res 420 32—38. 

Figure 2.4. In vivo measurement of blood-brain barrier (BBB) permeability, (a) Internal carotid artery perfusion technique (i) in the rat. Other branches of the carotid artery are ligated or electrically coagulated (o, occipital artery p, pterygopalatine artery). The external carotid artery (e) is cannulated and the common carotid artery (c) ligated. Perfusion time may range from 15 s to 10 min, depending on the test substance. It is necessary to subtract the intravascular volume, Vo, from (apparent volume of distribution), to obtain true uptake values and this may be achieved by inclusion of a vascular marker in the perfusate, for example labelled albumin. Time-dependent analysis of results in estimates of the unidirectional brain influx constant Ki (pi min which is equivalent within certain constraints to the PS product. BBB permeability surface area product PS can be calculated from the increase in the apparent volume of distribution Vd over time. Capillary depletion, i.e. separation of the vascular elements from the homogenate by density centrifugation, can discriminate capillary uptake from transcytosis. (b) i.v. bolus kinetics. The PS product is calculated from the brain concentration at the sampling time, T, and the area under the plasma concentration-time curve, AUC.

Broadwell RD (1989) Transcytosis of macromolecules through the blood-brain barrier A cell biological perspective and critical appraisal. Acta Neuropathol (Berl) 79 117-128. 

Broadwell RD (1993) Endothelial cell biology and the enigma of transcytosis through the blood-brain barrier. Adv Exp Med Biol 331 137-141. 

Broadwell RD, Banks WA (1993) Cell biological perspective for the transcytosis of peptides and proteins throngh the mammalian blood-brain flnid barriers. In The Blood-Brain Barrier (Pardridge WM, ed), pp 165-199. New York Raven Press, Ltd. 

Descamps L, Dehouck M-P, Torpier G, Cecchelli R. 1996. Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 39 1149-58... 

Mackic JB, Stins M, McComb JG, Calero M, Ghiso J, et al. 1998. Human blood-brain barrier receptors for Alzheimer s amyloid-beta 1-40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer. J. Clin. Invest. 1024 734 13... 

III). The tight tissue boundaries include the intestinal wall, skin, cornea, conjunctiva, blood-brain barrier, placental barrier, and blood-retina barrier. In leaky tissue boundaries (e.g. fenestrated endothelia, sinusoidal vessels, and tissue boundaries disrupted by the disease states such as inflammation), the nanoparticulates may pass the barrier by paracellular permeation. In specific cases, receptor-mediated transcytosis may be possible... 

Dehouck B. Fenart L, Dehouck MP. Pierce A, Torpier G, Cecchelli R. A new function for the LDL receptor transcytosis of LDL across the blood-brain barrier. J Cell Biol 1997 138 877-889. 

Traumatic brain injury, simulated by a model of closed head injury to mice, had also been shown to result in disruption of the BBB. The temporal resolution of this disruption was monitored by MRI in rats subjected to closed head injury. Blood-brain barrier disruption appeared immediately after the impact, and declined gradually, until full reversal to control levels 30 min post-injury. Opening of the BBB was similarly demonstrated in response to acute anticholinesterase exposure, however, low-level exposure has not yet been tested. BBB disruption under anticholinesterase exposure was proven to be seizure-dependent, as it could be blocked by the use of anticonvulsant agents. The anticholinesterase effect on BBB ultrastructure did not impair endothelial tight junctions. Yet, an increased number of endothelial vesicles were observed, suggesting increased transcytosis as the mechanism involved. ... 

Certain proteins, such as insulin, transferrin, and insulin-like growth factors, cross the blood-brain barrier by receptor-mediated transcytosis. Once the protein binds to its membrane receptor, the membrane containing the receptor-protein complex is endocytosed into the endothelial cell to form a vesicle. It is released on the other side of the endothelial cell. Absorptive-mediated transcytosis also can occur. It differs from receptor-mediated transcytosis in that the protein binds nonspecifically to the membrane and not to a distinct receptor. 

Pardridge, W.M. et al., 1990. Comparison of in vitro and in vivo models of drug transcytosis through the blood-brain barrier. The Journal of Pharmacology and Experimental Therapeutics. 253(2), pp. 884-891. 

Kratzer, I., et aL, Apolipoprotein A-I coating of protamine-oligonucleotide nanoparticles increases particle uptake and transcytosis in an in vitro model of the blood-brain barrier. Journal of Controlled Release, 117 (3) 301-311,2007. 

Villegas JC, Broad well RD (1993) Transcytosis of protein through the mammalian cerebral epithelium and endothelium II. Adsorptive transcytosis of WGA-HRP and the blood-brain and brain-blood barriers. J Neurocytol 22 67-80. 

---