Role of the blood–brain barrier in the evolution of feeding and cognition

Banks, William A.

doi:10.1111/j.1749-6632.2012.06568.x

Cited by 70 publications

(55 citation statements)

References 71 publications

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“…Physiological changes of the BBB occur throughout development [15] and during emotional responses [17–19] and other behaviors [19,20], and pathological changes of the BBB result from ischemic/hemorrhagic stroke [21,22], seizure [23], Alzheimer’s disease [24–26], Parkinson’s disease [27], HIV-associated neurocognitive disorders [28,29], multiple sclerosis [30], and obesity [20]. In addition, because the BBB is a major obstacle for drug delivery into the brain, its pharmacology has been investigated widely [8,9,31–35].…”

Section: Discussionmentioning

confidence: 99%

Distinct Patterns of Cerebral Extravasation by Evans Blue and Sodium Fluorescein in Rats

et al. 2013

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The Evans blue dye (EBD; 961 Da) and the sodium fluorescein dye (NaF; 376 Da) are commonly used inert tracers in blood-brain barrier (BBB) research. They are both highly charged low molecular weight (LMW) tracers with similar lipophobic profiles. Nevertheless, the EBD binds to serum albumin (69,000 Da) to become a high molecular weight (HMW) protein tracer when injected into the circulation, whereas the NaF remains an unbound small molecule in the circulation. In this study, rats were injected with equal doses of either EBD or NaF to monitor their blood and tissue distribution. The EBD was largely confined to the circulation with little accumulation in the peripheral organ and even less accumulation in the central tissue, whereas the NaF distributed more evenly between the blood and the peripheral organ but was also largely excluded from the central tissue. Importantly, the EBD crossed the BBB most effectively at the prefrontal cortex and the cerebellum, and most poorly at the striatum. In marked contrast, the NaF was evenly distributed throughout the brain. Finally, the EBD exhibited this same peculiar tissue distribution profile when administered by either bolus injection or slow infusion. Our study suggests that different regions of the brain are equally permeable to LMW inert dyes like the NaF, but are markedly different in permeability to HMW proteins such as EBD-labelled serum albumin.

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Section: Discussionmentioning

confidence: 99%

Distinct Patterns of Cerebral Extravasation by Evans Blue and Sodium Fluorescein in Rats

et al. 2013

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“…Insulin thus belongs to a category of peptides that have effects both on feeding and cognition, that category including leptin, ghrelin, glucagonlike peptide/exendin, melanocyte stimulating hormone, vasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide, secretion, cholecystokinin, substance P, and orexin A. The evolutionary underpinnings of this relation have been explored elsewhere (Banks, in press). …”

Section: Insulin Action In the Brain: Behavioral Effectsmentioning

confidence: 99%

Insulin in the brain: There and back again

Banks

Owen

Erickson

2012

Pharmacology & Therapeutics

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481

380

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Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule. Brain endothelial cells (BEC), the cells that form the vascular BBB and contain the transporter that translocates insulin from blood to brain, is itself regulated by insulin. The insulin transporter is altered by physiological and pathological factors including hyperglycemia and the diabetic state. The latter can lead to BBB disruption. Pericytes, pluripotent cells in intimate contact with the BEC, protect the integrity of the BBB and its ability to transport insulin. Most of insulin’s known actions within the CNS are mediated through two canonical pathways, the phosphoinositide-3 kinase (PI3)/Akt and Ras/mitogen activated kinase (MAPK) cascades. Resistance to insulin action within the CNS, sometimes referred to as diabetes mellitus type III, is associated with peripheral insulin resistance, but it is possible that variable hormonal resistance syndromes exist so that resistance at one tissue bed may be independent of that at others. CNS insulin resistance is associated with Alzheimer’s disease, depression, and impaired baroreceptor gain in pregnancy. These aspects of CNS insulin action and the control of its entry by the BBB are likely only a small part of the story of insulin within the brain.

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“…Central nervous system (CNS) effects of leptin include modulation of energy homeostasis, feeding behavior, and reproductive function. Central obesity and IR are associated with hyperleptinemia coupled with leptin resistance (LR) and reduced leptin transport across the BBB and into the hypothalamus and hippocampus [15,17,18]. The inverse correlation of fasting leptin with gray matter volume in brains from obese individuals as compared to lean individuals suggests an important trophic function.…”

Section: Crs and T2dm: Relationship To DCmentioning

confidence: 99%

“…The inverse correlation of fasting leptin with gray matter volume in brains from obese individuals as compared to lean individuals suggests an important trophic function. Importantly, impaired leptin transport across the BBB due to hypertriglyceridemia coupled with peripheral LR and hypothalamic LR may play an important role in the development and progression of obesity [18]. …”

Section: Crs and T2dm: Relationship To DCmentioning

confidence: 99%

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

et al. 2013

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The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term ‘diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions.

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Role of the blood–brain barrier in the evolution of feeding and cognition

Cited by 70 publications

References 71 publications

Distinct Patterns of Cerebral Extravasation by Evans Blue and Sodium Fluorescein in Rats

Distinct Patterns of Cerebral Extravasation by Evans Blue and Sodium Fluorescein in Rats

Insulin in the brain: There and back again

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

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