scholarly journals Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mladena Lalić-Popović ◽  
Velibor Vasović ◽  
Boris Milijašević ◽  
Svetlana Goločorbin-Kon ◽  
Hani Al-Salami ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Deoxycholic Acid ◽  
Brain Barrier ◽  
Brain Cells ◽  
Diabetic Patients ◽  
Acid Pretreatment ◽  
Blood Brain ◽  
Male Wistar Rats ◽  
Poor Nutrition

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB.

scholarly journals Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice is Associated with Pericyte and Blood–Brain Barrier Dysfunction

2021 ◽  
Author(s):  
Lu Lin ◽  
Lishan Huang ◽  
Lijing Wang ◽  
Yubin Wu ◽  
Zhou Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Blood Brain Barrier ◽  
Severe Hypoglycemia ◽  
Brain Barrier ◽  
Blue Staining ◽  
Diabetic Patients ◽  
Inflammatory Factor ◽  
Diabetic Mice ◽  
Blood Brain

Abstract Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (180 mg/kg). Further abdominal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.

scholarly journals An overview of nanomedicines for neuron targeting

Nanomedicine ◽  
2020 ◽  
Vol 15 (16) ◽  
pp. 1617-1636 ◽  
Author(s):  
Jesus Garcia-Chica ◽  
West Kristian D Paraiso ◽  
Shihori Tanabe ◽  
Dolors Serra ◽  
Laura Herrero ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neuronal Cells ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Brain Cells ◽  
Medical Treatments ◽  
Blood Brain

Medical treatments of neuron-related disorders are limited due to the difficulty of targeting brain cells. Major drawbacks are the presence of the blood–brain barrier and the lack of specificity of the drugs for the diseased cells. Nanomedicine-based approaches provide promising opportunities for overcoming these limitations. Although many previous reviews are focused on brain targeting with nanomedicines in general, none of those are concerned explicitly on the neurons, while targeting neuronal cells in central nervous diseases is now one of the biggest challenges in nanomedicine and neuroscience. We review the most relevant advances in nanomedicine design and strategies for neuronal drug delivery that might successfully bridge the gap between laboratory and bedside treatment in neurology.

scholarly journals 104. Functional Correlation of Brain Cells and Substances Known to Influence the Blood-Brain Barrier (BBB)

1963 ◽  
Vol 5 (0) ◽  
pp. 127-128
Author(s):  
Yohji HARA ◽  
Jun TOMINAGA ◽  
Toshihiko KASAHARA ◽  
Tsuneyuki NAKAZAWA
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Cells ◽  
Functional Correlation ◽  
Blood Brain

scholarly journals Human Immunodeficiency Virus Type 1 Infection Increases the In Vivo Capacity of Peripheral Monocytes To Cross the Blood-Brain Barrier into the Brain and the In Vivo Sensitivity of the Blood-Brain Barrier to Disruption by Lipopolysaccharide

2008 ◽  
Vol 82 (15) ◽  
pp. 7591-7600 ◽  
Author(s):  
Hongwei Wang ◽  
Jinglin Sun ◽  
Harris Goldstein
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Brain Barrier ◽  
Human Immunodeficiency Virus Type ◽  
Brain Barrier ◽  
Blood Brain ◽  
Immunodeficiency Virus ◽  
The Brain ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1), introduced into the brain by HIV-1-infected monocytes which migrate across the blood-brain barrier (BBB), infects resident macrophages and microglia and initiates a process that causes HIV-1-associated neurocognitive disorders. The mechanism by which HIV-1 infection circumvents the BBB-restricted passage of systemic leukocytes into the brain and disrupts the integrity of the BBB is not known. Circulating lipopolysaccharide (LPS), which can compromise the integrity of the BBB, is significantly increased in HIV-1-infected individuals. We hypothesized that HIV-1 infection increases monocyte capacity to migrate across the BBB, which is further facilitated by a compromise of BBB integrity mediated by the increased systemic LPS levels present in HIV-1-infected individuals. To investigate this possibility, we examined the in vivo BBB migration of monocytes derived from our novel mouse model, JR-CSF/EYFP mice, which are transgenic for both a long terminal repeat-regulated full-length infectious HIV-1 provirus and ROSA-26-regulated enhanced yellow fluorescent protein. We demonstrated that JR-CSF/EYFP mouse monocytes displayed an increased capacity to enter the brain by crossing either an intact BBB or a BBB whose integrity was partially compromised by systemic LPS. We also demonstrated that the JR-CSF mouse BBB was more susceptible to disruption by systemic LPS than the control wild-type mouse BBB. These results demonstrated that HIV-1 infection increased the ability of monocytes to enter the brain and increased the sensitivity of the BBB to disruption by systemic LPS, which is elevated in HIV-1-infected individuals. These mice represent a new in vivo system for studying the mechanism by which HIV-1-infected monocytes migrate into the brain.

Glucocorticoid and type 1 interferon interactions at the blood–brain barrier: relevance for drug therapies for multiple sclerosis

Neuroreport ◽  
2001 ◽  
Vol 12 (10) ◽  
pp. 2189-2193 ◽  
Author(s):  
Pieter J. Gaillard ◽  
Peter H. van der Meide ◽  
A. (Bert) G. de Boer ◽  
Douwe D. Breimer
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Type 1 Interferon ◽  
Blood Brain

scholarly journals Critical Considerations on Statin Therapy

2020 ◽  
pp. 1-2
Author(s):  
Erich Ebner
Keyword(s):  
Statin Therapy ◽  
Blood Brain Barrier ◽  
Clinical Experience ◽  
Cholesterol Metabolism ◽  
Brain Barrier ◽  
Brain Cells ◽  
Blood Brain ◽  
Significant Damage ◽  
The Brain

The clinical experience, backed up by chemical analyzes, such as case observations and statistics, shows that Statin therapy entails significant damage. The focus will be on the importance of cholesterol for the functionality of the brain. The fact that brain cells show a sensitive balance of cholesterol metabolism and have to regulate their needs independently, since the blood-brain barrier does not allow the circulating blood to permeate, has to re- examine the importance and consequences of Statin therapy

scholarly journals Altered susceptibility of the blood‐brain barrier to disruption in type 1 diabetes (685.2)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Jasmine Scott ◽  
Shu Yang ◽  
Denise Arrick ◽  
William Mayhan
Keyword(s):  
Type 1 Diabetes ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier

1991 ◽  
Vol 74 (3) ◽  
pp. 475-479 ◽  
Author(s):  
Edward A. Neuwelt ◽  
Michael A. Pagel ◽  
Richard D. Dix
Keyword(s):  
Blood Brain Barrier ◽  
Viral Vectors ◽  
Genetic Material ◽  
Brain Barrier ◽  
Content Type ◽  
Blood Brain ◽  
Viral Particles ◽  
Simplex Virus ◽  
Feline Model

✓ The present studies were undertaken to determine if viral particles can be delivered across the rat blood-brain barrier (BBB). Osmotic BBB modification with intracarotid mannitol (25%) was immediately followed by bolus intracarotid administration of 0.5 ml purified, ultraviolet-inactivated, herpes simplex virus type 1 endogenously labeled with 35S-labeled methionine (2.0 × 106 cpm, approximately 5 × 108 plaque-forming units/ml). After 60 minutes, intravascular virus was cleared by saline perfusion and the animals were sacrificed. A marked increase (fourfold, p ≤ 0.02) in radioactivity was observed in the ipsilateral brain hemisphere when compared to control animals without barrier modification. Administration of intravenous virus immediately after BBB modification displayed no difference in delivery when compared to intracarotid saline-infused controls (without BBB modification) suggesting the importance of a first-pass phenomenon. There were no significant differences in serum concentrations among intracarotid or intravenous groups. These preliminary studies suggest the possibility of delivering viral particles across the BBB with osmotic disruption, which may permit delivery of genetic material in replication-defective viral vectors in the feline model of GM2-gangliosidosis.

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