Permeability of the developing blood-brain barrier to 14C-mannitol using the rat in situ brain perfusion technique

Preston, Jane E.; Al‐Sarraf, Hameed; Segal, Malcolm B.

doi:10.1016/0165-3806(95)00060-q

Cited by 86 publications

(63 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). This is consistent with previous reports that L-Pro and Gly were limited to transport from the blood to the brain using brain-uptake methods (Preston et al, 1995;Benrabh and Lefauconnier, 1996). This is supported by the finding that the apparent L-Pro CL BBB, efflux value of 46.7 l/(min⅐g of brain), determined by a combination of the BEI method (Fig.…”

Section: Discussionsupporting

confidence: 92%

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

et al. 2002

View full text Add to dashboard Cite

Although system A is present at the blood-brain barrier (BBB), the physiological roles of system A have not been clarified. The efflux transport of the substrates of system A, such as L-proline (L-Pro), glycine (Gly), and ␣-methylaminoisobutyric acid (MeAIB), across the BBB was investigated using the in vivo Brain Efflux Index method. Over a period of 40 min, L 3 H]MeAIB uptake. In light of these observations, our results indicate that L-Pro and Gly are transported from the brain across the BBB, whereas MeAIB is retained in the brain. System A is involved in efflux transport for L-Pro at the BBB. The predominantly expressed ATA2 mRNA at the BBB may play a role in maintaining the concentration of small neutral amino acids and cerebral osmotic pressure in the brain under pathological conditions.The blood-brain barrier (BBB), which is formed by complex tight junctions of the brain capillary endothelial cells, segregates the circulating blood from interstitial fluid in the brain (Cornford, 1985). The BBB is well known to regulate not only the supply of nutrients and drugs to the brain from the circulating blood (Cornford, 1985;Pardridge et al., 1990), but also the efflux transport of compounds, such as P-glycoprotein, which transports anticancer and other drugs (Tsuji et al., 1992;Schinkel et al., 1994). Another transporter at the BBB is system A, a transporter of small neutral amino acids, which accepts L-alanine, L-proline, glycine, and ␣-methylaminoisobutyric acid (MeAIB) as substrates. It has been suggested that system A is present in the abluminal (brain) side of the BBB because MeAIB, which is a specific nonmetabolizable substrate for system A (Norman and Mann, 1986), is taken up in an Na ϩ -dependent manner from the brain side using isolated rat brain capillaries (Betz and Goldstein, 1978) and isolated abluminal membrane vesicles from bovine brain endothelial cells (Sanchez del Pino et al., 1995). Several investigations using brain-uptake methods have established that system A substrates undergo limited influx transport across the BBB (Oldendorf, 1971;Sershen and Lajtha, 1979). These investigations suggest that system A plays a role in the efflux transport of small neutral amino acids at the BBB to maintain their concentration in the brain (Betz and Goldstein, 1978). However, it does not fully explain this hypothesis, because the neutral amino acids are believed to be supplied from the circulating blood (Cornford, 1985). ReThis work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. It was also supported in part by the Suzuken Memorial Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Uehara Memorial Foundation, the Novartis Foundation (Japan) for the Promotion of Science, the Nakatomi Foundation, the Japan Society

show abstract

Section: Discussionsupporting

confidence: 92%

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

et al. 2002

View full text Add to dashboard Cite

show abstract

“…The radioactive content was determined, 5min per sample, in a liquid scintillation counter (LS-6500, Beckman, USA), and the number of counts per minute detected in the plasma and in the brain tissue were expressed in nanomoles of 5-HT, based on the counts in the working solution of known concentration (N8). Times in the order of 10-15min are commonly used in studies of this type in mammals (Buschiazzo et al, 1970;Vitte et al, 1988;Naylor et al, 1995;Preston et al, 1995;Perasso et al, 2003) and fish . If a substance passes the BBB it will actually be detectable in the brain long before 15min.…”

Section: -Ht and The Blood-brain Barriermentioning

confidence: 99%

Homeostasis of glucose in the rainbow trout (Oncorhynchus mykiss Walbaum): the role of serotonin

Tubío

Maceira

Aldegunde

2010

Journal of Experimental Biology

View full text Add to dashboard Cite

show abstract

“…At the set reoxygenation timepoints, the carotid arteries were cannulated with silicone tubing and the jugular veins were cut. The perfusion medium (Preston et al, 1995) consisted of Evans blue albumin (0.05 g·l −1 ) in a mammalian Ringer (NaCl 117.0 mM; KCl 4.7 mM; MgSO 4 (H 2 O) 0.8 mM; NaHCO 3 24.88 mM; KH 2 PO 4 1.2 mM; CaCl 2 (6H 2 O) 2.5 mM; D-glucose 10 mM; dextran (M.W. 70,000 da) 39 g·l −1 and bovine serum albumin 1 g·l −1 ), which was oxygenated with 95% O 2 , 5% CO 2 .…”

Section: In Situ Brain Perfusionmentioning

confidence: 99%

Reoxygenation stress on blood–brain barrier paracellular permeability and edema in the rat

Witt

Mark

Sandoval

et al. 2008

Microvascular Research

View full text Add to dashboard Cite

The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1hr) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 hr time course in conjunction with paracellular permeability, grey matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14 C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6−18hr time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 hr reoxygenation time points; and the second increase at only the 24 hr time point). Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, & IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White bloodcell counts showed significant decreases in lymphocytes (10 min-3 hr), increases in monocytes (10 min-3 hr & 12 hr), and increases in polymorphonuclear cells (1hr & 3 hr). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.

show abstract

Permeability of the developing blood-brain barrier to 14C-mannitol using the rat in situ brain perfusion technique

Cited by 86 publications

References 23 publications

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

Homeostasis of glucose in the rainbow trout (Oncorhynchus mykiss Walbaum): the role of serotonin

Reoxygenation stress on blood–brain barrier paracellular permeability and edema in the rat

Contact Info

Product

Resources

About