In situ brain perfusion reveals functional changes in the blood-brain barrier in mouse models of Sanfilippo syndrome Types A and B

2009 ◽  
Author(s):  
C.C. Pontikis ◽  
E. Zaccariotto ◽  
D.J. Begley
Keyword(s):  
Blood Brain Barrier ◽  
Mouse Models ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Sanfilippo Syndrome ◽  
Functional Changes ◽  
In Situ Brain Perfusion ◽  
Blood Brain

Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression

2003 ◽  
Vol 285 (6) ◽  
pp. H2820-H2831 ◽  
Author(s):  
Ken A. Witt ◽  
Karen S. Mark ◽  
Sharon Hom ◽  
Thomas P. Davis
Keyword(s):  
Protein Expression ◽  
Blood Brain Barrier ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Vascular Volume ◽  
Functional Changes ◽  
In Situ Brain Perfusion ◽  
Blood Brain ◽  
Junctional Protein

Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB permeability with associated alterations in tight junctional protein expression. These results suggest that H/R leads to reorganization of TJs and increased paracellular diffusion at the BBB, which is not a result of increased CBF, vascular volume change, or endothelial uptake of marker. Additionally, the tight junctional protein occludin had a shift in bands that correlated with functional changes (i.e., increased permeability) without significant change in expression of claudin-3, zonula occludens-1, or actin. H/R-induced changes in the BBB may result in edema and/or associated pathological outcomes.

scholarly journals Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique

2000 ◽  
Vol 279 (3) ◽  
pp. H1022-H1028 ◽  
Author(s):  
Hideyasu Murakami ◽  
Hitomi Takanaga ◽  
Hirotami Matsuo ◽  
Hisakazu Ohtani ◽  
Yasufumi Sawada
Keyword(s):  
Blood Brain Barrier ◽  
Brain Perfusion ◽  
External Carotid Artery ◽  
Brain Barrier ◽  
External Carotid ◽  
Perfusion Technique ◽  
Perfusion Rate ◽  
In Situ Brain Perfusion ◽  
Blood Brain

Here we present a method for measuring the permeability coefficient-surface area product ( PS) values at the blood-brain barrier in mice, using the in situ brain perfusion technique originally developed for rats by Takasato et al. ( Am J Physiol Heart Circ Physiol 247: H484–H493, 1984). Retrograde infusion into the right external carotid artery increased the carotid perfusion pressure in proportion to the perfusion rate. Intravascular volume and cerebral perfusion fluid flow at a perfusion rate of 1.0 ml/min in mice were similar to those in rats. In addition, the contribution of systemic blood to total flow in the hemisphere was small (only 3.2%). These findings indicated that this perfusion rate is suitable for mice. The PS values of more than 20 different compounds were determined in mice by using the in situ brain perfusion technique, and comparisons were made with data from rats. There was a close relationship (1:1) between the PS values in mice and rats, indicating that brain capillary permeabilities are similar in mice and rats.

Blood-brain barrier tight junctions are altered during a 72-h exposure to λ-carrageenan-induced inflammatory pain

2002 ◽  
Vol 283 (4) ◽  
pp. H1531-H1537 ◽  
Author(s):  
J. D. Huber ◽  
V. S. Hau ◽  
L. Borg ◽  
C. R. Campos ◽  
R. D. Egleton ◽  
...  
Keyword(s):  
Western Blot ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Inflammatory Pain ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Brain Uptake ◽  
In Situ Brain Perfusion ◽  
Blood Brain

In this study, we examined the effect of λ-carrageenan-induced inflammatory pain on the functional and structural properties of the rat blood-brain barrier (BBB) over a 72-h time period. Systemic inflammation was induced by an intraplantar injection of 3% λ-carrageenan into the right hind paw of female Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed λ-carrageenan significantly increased brain uptake of [14C]sucrose at 1, 3, 6, and 48 h (139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis insured the increased brain uptake was due to increased BBB permeability and not vascular trapping. Western blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at 1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin expression was significantly reduced at 1, 3, 6, 12, and 48 h. This investigation demonstrated that λ-carrageenan-induced inflammatory pain elicits a biphasic increase in BBB permeability with the first phase occurring from 1–6 h and the second phase occuring at 48 h. Furthermore, changes in BBB function are correlated with altered tight junctional protein expression of occludin and ZO-1. Changes in the structure of tight junctions may have important clinical ramifications concerning central nervous system homeostasis and therapeutic drug delivery.

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