Ischemia-induced hyperglycemia: Consequences, neuroendocrine regulation, and a role for RAGE

Weil, Zachary M.

doi:10.1016/j.yhbeh.2012.04.001

Cited by 22 publications

(17 citation statements)

References 89 publications

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“…Hyperglycemia may also promote ischemic injury by other mechanisms, including enhanced glucose-sodium exchange and formation of abnormal protein glycosylation and advanced glycation products 23–25 , but a definitive role for these processes in acute ischemic injury has not yet been established. Hyperglycemia is also strongly associated with an intensified post-ischemic inflammatory response, but it has been difficult to unravel whether the increased inflammation is a cause or result of increased ischemic brain injury.…”

Section: Effects Of Blood Glucose Concentrations On Ischemic Brain Inmentioning

confidence: 99%

Opposing Effects of Glucose on Stroke and Reperfusion Injury

Robbins

Swanson

2014

Stroke

114

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Section: Effects Of Blood Glucose Concentrations On Ischemic Brain Inmentioning

confidence: 99%

Opposing Effects of Glucose on Stroke and Reperfusion Injury

Robbins

Swanson

2014

Stroke

114

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“…Type 2 diabetes can negatively impact the outcome of stroke (ischemic brain damage); in fact increases the risk of stroke, as demonstrated in vivo in type 2 diabetic mice [15]. Conversely, hyperglycemia is also associated with high levels of mortality and morbidity during cerebral ischemia, perhaps, caused by increased cerebral hematoma expansion [14] and higher risk of cerebral hemorrhage due to tissue Plasminogen Activator (tPA) activation and superoxide production damaging the BBB [17] Recent studies also evoke a role for the AGE-RAGE system activated by hyperglycemia leading to a further enhancement of oxidative stress and amplification of inflammatory signals from nearby leukocytes [18,19]. Improved glycemic control in these patients seem to ameliorate these pathological conditions [10] however, rapid normalization of plasma glucose levels in hyperglycemic subjects can lead to cerebral hypoglycemia thus favoring cognitive decline [20-25].…”

Section: Introductionmentioning

confidence: 99%

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

Prasad

Sajja

Naik

et al. 2014

J Pharmacovigilance

144

106

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A host of diabetes-related insults to the central nervous system (CNS) have been clearly documented in type-1 and -2 diabetic patients as well as experimental animal models. These host of neurological disorders encompass hemodynamic impairments (e.g., stroke), vascular dementia, cognitive deficits (mild to moderate), as well as a number of neurochemical, electrophysiological and behavioral alterations. The underlying causes of diabetes-induced CNS complications are multifactorial and are relatively little understood although it is now evident that blood-brain barrier (BBB) damage plays a significant role in diabetes-dependent CNS disorders. Changes in plasma glucose levels (hyper- or hypoglycemia) have been associated with altered BBB transport functions (e.g., glucose, insulin, choline, amino acids, etc.), integrity (tight junction disruption), and oxidative stress in the CNS microcapillaries. Last two implicating a potential causal role for upregulation and activation of the receptor for advanced glycation end products (RAGE). This type I membrane-protein also transports amyloid-beta (Aβ) from the blood into the brain across the BBB thus, establishing a link between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD, also referred to as “type 3 diabetes”). Hyperglycemia has been associated with progression of cerebral ischemia and the consequent enhancement of secondary brain injury. Difficulty in detecting vascular impairments in the large, heterogeneous brain microvascular bed and dissecting out the impact of hyper- and hypoglycemia in vivo has led to controversial results especially with regard to the effects of diabetes on BBB. In this article, we review the major findings and current knowledge with regard to the impact of diabetes on BBB integrity and function as well as specific brain microvascular effects of hyper- and hypoglycemia.

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“…Interpretation of this finding is difficult since there is currently inadequate knowledge about the changes that occur within the cerebral vasculature of the diabetic brain in response to hyperglycemia or of the mechanisms associated with UO. Increased BBB leakage has been associated with an increased hemorrhagic transformation, which is believed to reflect tissue plasminogen activator activation [34] , increased levels of cerebral edema reflecting changes in osmotic homoeostasis due to leakage of large molecules through the impaired BBB [35] , and increased inflammatory signaling [36] with swelling of astroglial cells [30] . In a recent review, Ergul et al [26] identified a series of mechanisms associated with the failure of neovascularization and poor outcome in DS, including increased incidence of hemorrhagic transformation, activation of the pro-apoptotic p38MAP kinase pathway and increased endothelial cell death.…”

Section: Discussionmentioning

confidence: 99%

Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

Jackson

et al. 2016

Cerebrovasc Dis

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Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.

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Ischemia-induced hyperglycemia: Consequences, neuroendocrine regulation, and a role for RAGE

Cited by 22 publications

References 89 publications

Opposing Effects of Glucose on Stroke and Reperfusion Injury

Opposing Effects of Glucose on Stroke and Reperfusion Injury

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

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