Vascular Pathology and Blood-Brain Barrier Disruption in Cognitive and Psychiatric Complications of Type 2 Diabetes Mellitus

Serlin, Yonatan; Levy, Jaime; Shalev, Hadar

doi:10.1155/2011/609202

Cited by 84 publications

(64 citation statements)

References 138 publications

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“…Stroke triggers an inflammatory reaction for hours after the onset of a stroke, and this inflammation plays a central role in the pathogenesis of neuronal injury in ischemic stroke and especially in diabetic stroke [38]. In our experiments, CHS decreased the expression of IL-6 and TNF-α during brain I/R injury, demonstrating that CHS can exhibit protective effects during brain I/R injury through inhibiting the inflammatory cascade.…”

Section: Discussionsupporting

confidence: 51%

Chikusetsu Saponin IVa Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice via Adiponectin-Mediated AMPK/GSK-3β Pathway In Vivo and In Vitro

et al. 2015

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Diabetes mellitus substantially increases the risk of stroke and enhances brain's vulnerability to ischemia insult. In a previous study, Chikusetsu saponin IVa (CHS) pretreatment was proved to protect the brain from cerebral ischemic in normal stroke models. Whether CHS could attenuate cerebral ischemia/reperfusion (I/R) injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were injected streptozotocin to induce diabetes. After that, the mice were pretreated with CHS for 1 month, and then, focal cerebral ischemia was induced following 24-h reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. Apoptosis was analyzed by caspase-3, Bax, and Bcl-2 expression. Downstream molecules of adiponectin (APN) were investigated by Western blotting. The results showed that CHS reduced infarct size, improved neurological outcomes, and inhibited cell injury after I/R. In addition, CHS pretreatment increased APN level and enhanced neuronal AdipoR1, adenosine monophosphate-activated protein kinase (AMPK), and glycogen synthase kinase 3 beta (GSK-3β) expression in a concentration-dependent manner in diabetic mice, and these effects were abolished by APN knockout (KO). In vitro test, CHS treatment also alleviated PC12 cell injury and apoptosis, evidenced by reduced tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA) and caspase-3 expression, and Bax/Bcl-2 ratio in I/R injured cells. Moreover, CHS enhanced AdipoR1, AMPK, and GSK-3β expression in a concentration-dependent manner. Likewise, short interfering RNA (sinRNA) knockdown of liver kinase B1 (LKB1), an upstream kinase of AMPK, reduced the ability of CHS in protecting cells from I/R injury. Furthermore, this LKB1-dependent cellular protection resulted from AdipoR1 and APN activation, as supported by the experiment using sinRNA knockdown of AdipoR1 and APN. Thus, CHS protected brain I/R in diabetes through AMPK-mediated phosphorylation of GSK-3β downstream of APN-LKB1 pathway.

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Section: Discussionsupporting

confidence: 51%

Chikusetsu Saponin IVa Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice via Adiponectin-Mediated AMPK/GSK-3β Pathway In Vivo and In Vitro

et al. 2015

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“…In addition to loss of BBB integrity, there is increasing evidence that hypoperfusion and/or loss of neurovascular coupling may be a key pathway whereby oxidative stress connects vascularrelated diseases to cognitive impairment (45,55). Indeed, evidence suggests that diabetes-induced cognitive decline may be induced via disruption of neurovascular coupling, with physiological impairment arising from both cerebrovascular elements and also glial cells (61,83). In this light, it is important to note that NADPH oxidase is a major player in both endothelial and glial physiology.…”

Section: E400mentioning

confidence: 99%

NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet

Pepping

Freeman

Gupta

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Pepping JK, Freeman LR, Gupta S, Keller JN, Bruce-Keller AJ. NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet. Am J Physiol Endocrinol Metab 304: E392-E404, 2013. First published December 11, 2012 doi:10.1152/ajpendo.00398.2012.-The consumption of high-fat/ calorie diets in modern societies is likely a major contributor to the obesity epidemic, which can increase the prevalence of cancer, cardiovascular disease, and neurological impairment. Obesity may precipitate decline via inflammatory and oxidative signaling, and one factor linking inflammation to oxidative stress is the proinflammatory, pro-oxidant enzyme NADPH oxidase. To reveal the role of NADPH oxidase in the metabolic and neurological consequences of obesity, the effects of high-fat diet were compared in wild-type C57Bl/6 (WT) mice and in mice deficient in the NAPDH oxidase subunit NOX2 (NOX2KO). While diet-induced weight gains in WT and NOX2KO mice were similar, NOX2KO mice had smaller visceral adipose deposits, attenuated visceral adipocyte hypertrophy, and diminished visceral adipose macrophage infiltration. Moreover, the detrimental effects of HFD on markers of adipocyte function and injury were attenuated in NOX2KO mice; NOX2KO mice had improved glucose regulation, and evaluation of NOX2 expression identified macrophages as the primary population of NOX2-positive cells in visceral adipose. Finally, brain injury was assessed using markers of cerebrovascular integrity, synaptic density, and reactive gliosis, and data show that high-fat diet disrupted marker expression in WT but not NOX2KO mice. Collectively, these data indicate that NOX2 is a significant contributor to the pathogenic effects of high-fat diet and reinforce a key role for visceral adipose inflammation in metabolic and neurological decline. Development of NOX-based therapies could accordingly preserve metabolic and neurological function in the context of metabolic syndrome. brain injury; metabolic syndrome; NADPH oxidase; obesity

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“…A recent review16 discussed how type 2 diabetes mellitus or hyperglycaemia causes changes in the blood brain barrier permeability and inflammatory process. In type 2 diabetes mellitus, there is an activation of neuroendocrine and inflammatory response that is responsible for the induction of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Psychosis post corona radiata and lentiform nucleus infarction

Abdullah

Saini²,

Sharip

et al. 2015

BMJ Case Reports

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Complications of stroke can include neuropsychiatric symptoms. However, post-stroke psychosis is rare. We report a case where an acute presentation of psychosis, depression and fluctuating cognitive impairment in a middle-aged man turned out to be related to a silent brain infarction. The patient had a background of poorly controlled type 2 diabetes mellitus with glycated haemoglobin level of 9.0-11.0%, hypertension and ischaemic heart disease. His CT brain results showed multifocal infarct with hypodensities at bilateral lentiform nucleus and bilateral corona radiata. His strong genetic predisposition of psychosis and a history of brief psychotic disorder with complete remission 3 years prior to the current presentation might possibly contribute to his post-stroke atypical neuropsychiatric presentation, and posed diagnostic challenges. He showed marked improvement with risperidone 6 mg nocte, chlorpromazine 50 mg nocte and fluvoxamine of 200 mg nocte. The need of comprehensive treatments to modify his stroke risk factors was addressed.

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Vascular Pathology and Blood-Brain Barrier Disruption in Cognitive and Psychiatric Complications of Type 2 Diabetes Mellitus

Cited by 84 publications

References 138 publications

Chikusetsu Saponin IVa Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice via Adiponectin-Mediated AMPK/GSK-3β Pathway In Vivo and In Vitro

Chikusetsu Saponin IVa Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice via Adiponectin-Mediated AMPK/GSK-3β Pathway In Vivo and In Vitro

NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet

Psychosis post corona radiata and lentiform nucleus infarction

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