Regional Studies of Blood—Brain Barrier Transport of Glucose and Leucine in Awake and Anesthetized Rats

LaManna, Joseph C.; Harik, Sami I.

doi:10.1038/jcbfm.1986.128

Cited by 44 publications

(18 citation statements)

References 36 publications

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“…Weight gain was less in the KG group than in the other two groups, but there were no significant differences among diet groups. The physiological data were similar to those we previously reported in chloral hydrate-anesthetized rats (16,17,35).…”

Section: Effect Of Ketosis On Plasma ␤-Hb Concentrationsupporting

confidence: 90%

“…The trends in regional blood flows in the STD group showed that blood flow was highest in the cortex [1.1 (SD 0.1)] and brain stem (1.4 Ϯ 0.2) and lowest in the cerebellum [0.90 (SD 0.2)]. Regional blood flows measured in this study were comparable to those previously reported using the blood flow-indicator method (16,17,35,44).…”

supporting

confidence: 85%

“…Subsequent work in rats led to a modified uptake method, known as the single-pass dual-label isotope-indicator (unidirectional tracer) method, which allows for quantitation of substrates, such as glucose, lactate, or ketones, at the endothelial boundary of the BBB, as well as simultaneous estimation of blood flow (7,16,33).…”

mentioning

confidence: 99%

“…Disintegrations per minute (dpm) in brain tissue samples were corrected (dpmcorrect) for intravascular compartment volumes (Vpl) as follows: dpmcorrect ϭ dpmtissue Ϫ (dpmpl/l ϫ Vpl ϫ tissue wt) (16).…”

mentioning

confidence: 99%

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Diet-induced ketosis increases capillary density without altered blood flow in rat brain

Puchowicz¹,

Xu²,

Sun³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Puchowicz MA, Xu K, Sun X, Ivy A, Emancipator D, LaManna JC. Diet-induced ketosis increases capillary density without altered blood flow in rat brain. Am J Physiol Endocrinol Metab 292: E1607-E1615, 2007. First published February 6, 2007; doi:10.1152/ajpendo.00512.2006.-It is recognized that ketone bodies, such as R-␤-hydroxybutyrate (␤-HB) and acetoacetate, are energy sources for the brain. As with glucose metabolism, monocarboxylate uptake by the brain is dependent on the function and regulation of its own transporter system. We concurrently investigated ketone body influx, blood flow, and regulation of monocarboxylate transporter (MCT-1) and glucose transporter (GLUT-1) in diet-induced ketotic (KG) rat brain. Regional blood-to-brain ␤-HB influx (mol⅐g Ϫ1 ⅐min Ϫ1) increased 40-fold with ketosis (4.8 Ϯ 1.8 plasma␤-HB; mM) in all regions compared with the nonketotic groups (standard and no-fat diets); there were no changes in regional blood flow. Immunohistochemical staining revealed that GLUT-1 density (number/mm 2 ) in the cortex was significantly elevated (40%) in the ketotic group compared with the standard and no-fat diet groups. MCT-1 was also markedly (3-fold) upregulated in the ketotic group compared with the standard diet group. In the standard diet group, 40% of the brain capillaries stained positive for MCT-1; this amount doubled with the ketotic diet. Western blot analysis of isolated microvessels from ketotic rat brain showed an eightfold increase in GLUT-1 and a threefold increase in MCT-1 compared with the standard diet group. These data suggest that diet-induced ketosis results in increased vascular density at the blood-brain barrier without changes in blood flow. The increase in extraction fraction and capillary density with increased plasma ketone bodies indicates a significant flux of substrates available for brain energy metabolism. ketone bodies; monocarboxylate transporter-1; GLUT-1; ␤-hydroxybutyrate; brain metabolism; blood-brain barrier GLUCOSE IS THE MAJOR METABOLIC FUEL for the mammalian brain (37, 41), but alternate energy substrates such as ketone bodies, e.g., R-␤-hydroxybutyrate (␤-HB) and acetoacetate (6,19,29,39), serve as efficient metabolic fuel sources for the brain. This is especially important under certain nutritional conditions, such as fasting, starvation (28), feeding of a high-fat diet (24, 26), and early development and throughout the suckling period (2, 25, 42). Clinicians and investigators have been interested in ketone bodies as therapeutic agents for the treatment of hypoglycemia, seizure disorders, and Alzheimer's and Parkinson's diseases and as alternatives to high-lipid parenteral and enteral feedings (5,14,43).Similar in chemical structure to lactate and pyruvate (intermediates of glycolysis), ketones are metabolized by the brain, especially neonatal mammalian brain (1,2,20,40). These short-chain acids are referred to as monocarboxylates, and, as with glucose metabolism, systemic delivery of these substrates and availability for neuronal uptake are highly depe...

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Section: Effect Of Ketosis On Plasma ␤-Hb Concentrationsupporting

confidence: 90%

supporting

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Diet-induced ketosis increases capillary density without altered blood flow in rat brain

Puchowicz¹,

Xu²,

Sun³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Sev eral studies have concluded that the vascular vol ume of the cerebellum is from 10 to 60% higher than that in the cerebrum (see Table O. The methods used to measure vascular volume in these studies employed radiolabeled tracers such as e4C]inulin (LaManna and Harik, 1986), eH]sucrose (Picozzi et aI., 1985), 125I_serum albumin (Cremer and Seville, 1983;Pluta et aI., 1989), and/or 51C-Iabeled red blood cells (Johanson, 1980;Cremer and Seville, 1983;Pluta et aI., 1989). The important feature that these techniques have in common is that the tracer cerebellum and cerebrum.…”

mentioning

confidence: 99%

The Difference in Vascular Volume between Cerebrum and Cerebellum is in the Pia Mater

Holash

Sugamori

Stewart

1990

J Cereb Blood Flow Metab

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Summary: Previous studies using intravascular tracers have shown that the apparent vascular volume in the cer ebellum is 10--60% higher than that in the cerebrum. We questioned whether the extravascular volume in the cer ebellum could be accounted for by the vasculature of the pia mater that covers its highly infolded surface. Esti mates of vascular volume were made using a previously reported point-counting method. Two counts were done: one in which only intraparenchymal vessels were in cluded, and a second one in which both intraparenchymal vessels and pial vessels were included. We found no dif ferences in intraparenchymal vascular volume between (Fenstermacher et aI., 1988). Sev eral studies have concluded that the vascular vol ume of the cerebellum is from 10 to 60% higher than that in the cerebrum (see Table O. The methods used to measure vascular volume in these studies employed radiolabeled tracers such as e4C]inulin (LaManna and Harik, 1986), eH]sucrose (Picozzi et aI., 1985), 125I_serum albumin (Cremer and Seville, 1983; Pluta et aI., 1989), and/or 51C-Iabeled red blood cells (Johanson, 1980;Cremer and Seville, 1983; Pluta et aI., 1989). The important feature that these techniques have in common is that the tracer 432 cerebellum and cerebrum. When the pial vessels are in cluded, however, the cerebral vascular volume increases by <6%, whereas the cerebellar vascular volume in creases by >30%. We suggest that the higher cerebellar vascular volume measured using intravascular tracers is due to inclusion of the pial vasculature. Since pial vessels do not express blood-brain barrier characteristics as prominently as intraparenchymal vessels, we further sug gest that estimates of barrier permeability in cerebellum should not be made using simple models developed for cerebral tissue. Key Words: Vascular volume-Pia mater -Cerebellum-Cerebrum-Blood-brain barrier.has a negligible permeability across the intact blood-brain barrier, and so is confined to the vessel lumen. Therefore, the total content of tracer in the tissue is a measurement of the vascular compart ment.Preliminary morphometric studies on intraparen chymal vessels of adult mice (J. A. Holash and P. A. Stewart, unpublished results) failed to con firm a higher vascular volume in cerebellum com pared to cerebrum. We questioned, therefore, where in the cerebellum the additional vascular tracer measured in the studies cited above could be located. In harvesting fragments of brain tissue for measurement of tracer content, the pia mater is usu ally left attached to the surface, although some au thors remove or avoid the larger pial vessels (Cre mer and Seville, 1983; Picozzi et aI., 1985; Pluta et aI., 1989). It is difficult to remove the pia entirely from the smooth surface of the cerebrum and ex tremely difficult to remove it from the highly in folded surface of the cerebellum. It seemed possible that the apparently increased vascular volume in the cerebellum could be due to the inclusion of its rich pial vasculature.

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Endothelial cell heterogeneity of blood‐brain barrier gene expression along the cerebral microvasculature

Macdonald

Murugesan

Pachter

2009

J of Neuroscience Research

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The blood-brain barrier (BBB) refers to the network of microvessels that selectively restricts the passage of substances between the circulation and the central nervous system (CNS). This microvascular network is comprised of arterioles, capillaries and venules, yet the respective contribution of each of these to the BBB awaits clarification. In this regard, it has been postulated that brain microvascular endothelial cells (BMEC) from these different tributaries might exhibit considerable heterogeneity in form and function, with such diversity underlying unique roles in physiological and pathophysiological processes. Means to begin exploring such endothelial differences in situ, free from caveats associated with cell isolation and culturing procedures, are crucial to comprehending the nature and treatment of CNS diseases with vascular involvement. Here, the recently validated approach of immuno-laser capture microdissection (immuno-LCM) coupled to quantitative real-time PCR (qRT-PCR) was used to analyze gene expression patterns of BMEC retrieved in situ from either capillaries or venules. From profiling 87 genes known to play a role in BBB function and/or be enriched in isolated brain microvessels, results imply that most BBB properties reside in both segments, but that capillaries preferentially express some genes related to solute transport, while venules tend toward higher expression of an assortment of genes involved in inflammatory-related tasks. Fuller appreciation of such heterogeneity will be critical for efficient therapeutic targeting of the endothelium and the management of CNS disease.

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Regional Studies of Blood—Brain Barrier Transport of Glucose and Leucine in Awake and Anesthetized Rats

Cited by 44 publications

References 36 publications

Diet-induced ketosis increases capillary density without altered blood flow in rat brain

Diet-induced ketosis increases capillary density without altered blood flow in rat brain

The Difference in Vascular Volume between Cerebrum and Cerebellum is in the Pia Mater

Endothelial cell heterogeneity of blood‐brain barrier gene expression along the cerebral microvasculature

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