Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats

Huber, Jason D.; VanGilder, Reyna; Houser, Kimberly

doi:10.1152/ajpheart.00489.2006

Cited by 172 publications

(149 citation statements)

References 67 publications

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“…Increased BBB permeability was detected in patients with type II diabetes (Starr et al, 2003). Similarly, streptozotocin-induced diabetes in adult rats was associated with increases in permeability to small molecules, but similar to our findings, the changes were region specific with the largest changes occurring in the midbrain (Huber et al, 2006). The increases in BBB permeability in streptozotocin-induced diabetes appear to be related to a loss of tight junction proteins possibly resulting from increases in plasma matrix metalloproteinase activity and not from hyperglycemia alone (Hawkins et al, 2007).…”

Section: Discussionsupporting

confidence: 89%

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

Stonestreet

Sadowska

Hanumara

et al. 2011

J Cereb Blood Flow Metab

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We examined the effects of hyperglycemic hyperosmolality on blood-brain barrier (BBB) permeability during development. We hypothesized that the barrier becomes more resistant to hyperglycemic hyperosmolality during development, and the immature BBB is more resistant to glucose than to mannitol hyperosmolality. We quantified the BBB response to hyperosmolality with the blood-to-brain transfer constant (K i ) in immature fetuses, premature, and newborn lambs. K i increased as a function of increases in osmolality. A segmented regression model described the relationship between K i and osmolality. At lower osmolalities, changes in K i were minimal but after a threshold, increases were linear. We examined responses of K i to hyperglycemic hyperosmolality by comparing the thresholds and slopes of the second regression segments. Lower thresholds and steeper slopes indicate greater vulnerability to hyperosmolality. Thresholds increased (P < 0.05) during development in pons and superior colliculus. Thresholds were higher (P < 0.05) during glucose than mannitol hyperosmolality in thalamus, superior colliculus, inferior colliculus and medulla of premature lambs, and in cerebrum and cerebellum of newborns. We conclude that BBB permeability increased as a function of changes in glucose osmolality, the barrier becomes more resistant to glucose hyperosmolality in two brain regions during development, and the barrier is more resistant to glucose than to mannitol hyperosmolality in some brain regions of premature and newborn lambs.

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Section: Discussionsupporting

confidence: 89%

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

Stonestreet

Sadowska

Hanumara

et al. 2011

J Cereb Blood Flow Metab

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“…39 Huber et al clearly showed time-dependent, molecular weight-dependent failure of barrier function using streptozotocin-induced diabetic rats. 40 In that study, they demonstrated that changes in BBB permeability were region C]-sucrose to evaluate the molecule size effect on BBB permeability. Interestingly, total albumin extravasation did not change in diabetic rats compared with controls, indicating that overall the BBB remained intact.…”

Section: Basic Experimentsmentioning

confidence: 98%

Neurovascular Coupling in Cognitive Impairment Associated With Diabetes Mellitus

Mogi

Horiuchi

2011

Circ J

110

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Although it is feared that diabetes-induced cognitive decline will become a major clinical problem worldwide in the future, the detailed pathological mechanism is not well known. Because patients with diabetes have various complications of vascular disease, with not only macrovascular but also microvascular disorders, vascular disorders in the brain are considered to be one of the mechanisms in diabetes-induced cognitive impairment. Indeed, disruption of the blood - brain barrier (BBB) has been observed in some diabetic patients and experimental diabetes models. Moreover, white matter lesions, part of the evidence of BBB dysfunction, are reported to be observed more frequently in patients with diabetes. Animal studies demonstrate that diabetes enhances BBB permeability through a decrease in the level of tight junction proteins and an increase in matrix metalloproteinase activity. However, there are several reports indicating that BBB disruption does not occur with diabetes. Therefore, the association of BBB breakdown with diabetes-induced cognitive impairment is not conclusive. Recently, neuronal diseases involving dementia have been induced experimentally through dysfunction of neurovascular coupling, which involves blood vessels, astrocytes and neutrons. Diabetes-induced cognitive decline may be induced via disruption of neurovascular coupling, with not only vascular disorder but also impairment of astrocytic trafficking. Here, the relation between vascular disorder and cognitive impairment in diabetes is discussed. (Circ J 2011; 75: 1042 - 1048

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“…Metabolic abnormalities such as the long-lasting increase in blood glucose level, dyslipidemia, insulin resistance, hypertension and oxidative stress are common in diabetes mellitus. According to recent data, diabetes is a predisposing factor for Alzheimer disease (1), as older adults with type 2 diabetes sometimes develop cognitive impairments due to the impairment of insulin signaling and toxic accumulation of Amyloid Beta (Aβ) (2). The most affected parts are memory and mental processing speed, while cognitive skills such as attention, problem solving and general intelligence remain intact (3).…”

mentioning

confidence: 99%

Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

Ghasemi¹,

Zendehbad²,

Zabihi³

et al. 2016

Balkan Med J

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Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob) is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ)-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1-control, 2-diabetic, and 3-diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg) intraperitoneally (i.p). The animals received leptin (0.1 mg/kg) or saline subcutaneously (s.c) for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001) and decreased with leptin treatment (p<0.01 & p<0.001 respectively); also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively) in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats. Keywords: Leptin, spatial memory, streptozotocin

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Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats

Cited by 172 publications

References 67 publications

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

Neurovascular Coupling in Cognitive Impairment Associated With Diabetes Mellitus

Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

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