Cerebrovascular and Brain Microanatomy in Spontaneously Hypertensive Rats with Streptozotocin‐Induced Diabetes

Tomassoni, Daniele; Bellagamba, Gauthier; Postacchini, Demetrio; Venarucci, D; Amenta, Francesco

doi:10.1081/ceh-120034136

Cited by 18 publications

(18 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47,9 Therefore, we will mainly focus on diabetes induced changes in the cerebral microvessels. Numerous studies, mostly using streptozotocin (STZ)-induced T1D model, have reported that there is thickening of the cerebral microvascular basement membrane characterized by collagen deposition and amorphous nodules described as “cotton tufts.” 48,49,50,51,52,53 The widening of the basement membrane compromises the integrity of adjacent vascular smooth muscle cells, pericytes and astrocytic end feet that sit on the basement membrane and serve as a functional bridge between the vasculature and neuronal cells of the brain. 51 There is diffuse swelling of the astrocytic endfeet 50,51 and vascular smooth muscle mitochondria and endoplasmic reticulum.…”

Section: Summary Of Clinical Evidencementioning

confidence: 99%

Cerebrovascular Complications of Diabetes: Focus on Stroke

Ergul

Kelly-Cobbs

Abdalla

et al. 2012

EMIDDT

164

103

View full text Add to dashboard Cite

Cerebrovascular complications make diabetic patients 2–6 times more susceptible to a stroke event and this risk is magnified in younger individuals and in patients with hypertension and complications in other vascular beds. In addition, when patients with diabetes and hyperglycemia experience an acute ischemic stroke they are more likely to die or be severely disabled and less likely to benefit from the one FDA-approved therapy, intravenous tissue plasminogen activator. Experimental stroke models have revealed that chronic hyperglycemia leads to deficits in cerebrovascular structure and function that may explain some of the clinical observations. Increased edema, neovascularization and protease expression as well as altered vascular reactivity and tone may be involved and point to potential therapeutic targets. Further study is needed to fully understand this complex disease state and the breadth of its manifestation in the cerebrovasculature.

show abstract

Section: Summary Of Clinical Evidencementioning

confidence: 99%

Cerebrovascular Complications of Diabetes: Focus on Stroke

Ergul

Kelly-Cobbs

Abdalla

et al. 2012

EMIDDT

164

103

View full text Add to dashboard Cite

show abstract

“…MRI revealed significantly increased ventricular volume in SHR compared to WKY at 3 months of age [61]. There are fewer neurons in these brain areas compared to WKY [62-64]. …”

Section: Introductionmentioning

confidence: 99%

Animal models of attention-deficit hyperactivity disorder

2005

View full text Add to dashboard Cite

Although animals cannot be used to study complex human behaviour such as language, they do have similar basic functions. In fact, human disorders that have animal models are better understood than disorders that do not. ADHD is a heterogeneous disorder. The relatively simple nervous systems of rodent models have enabled identification of neurobiological changes that underlie certain aspects of ADHD behaviour. Several animal models of ADHD suggest that the dopaminergic system is functionally impaired. Some animal models have decreased extracellular dopamine concentrations and upregulated postsynaptic dopamine D1 receptors (DRD1) while others have increased extracellular dopamine concentrations. In the latter case, dopamine pathways are suggested to be hyperactive. However, stimulus-evoked release of dopamine is often decreased in these models, which is consistent with impaired dopamine transmission. It is possible that the behavioural characteristics of ADHD result from impaired dopamine modulation of neurotransmission in cortico-striato-thalamo-cortical circuits. There is considerable evidence to suggest that the noradrenergic system is poorly controlled by hypofunctional α2-autoreceptors in some models, giving rise to inappropriately increased release of norepinephrine. Aspects of ADHD behaviour may result from an imbalance between increased noradrenergic and decreased dopaminergic regulation of neural circuits that involve the prefrontal cortex. Animal models of ADHD also suggest that neural circuits may be altered in the brains of children with ADHD. It is therefore of particular importance to study animal models of the disorder and not normal animals. Evidence obtained from animal models suggests that psychostimulants may not be acting on the dopamine transporter to produce the expected increase in extracellular dopamine concentration in ADHD. There is evidence to suggest that psychostimulants may decrease motor activity by increasing serotonin levels. In addition to providing unique insights into the neurobiology of ADHD, animal models are also being used to test new drugs that can be used to alleviate the symptoms of ADHD.

show abstract

“…Chronic hyperglycemia, which further alters membrane permeability (26,27) and decreases regional blood flow, may lead to permanent cell damage (25). Therefore, diabetes seems to be associated with progressive metabolic disturbance in the cerebrovascular bed that may affect blood flow and accelerate the white matter degeneration.…”

Section: Multiple Regression Analysismentioning

confidence: 99%

“…Diabetes alters the glucose and insulin transfer across the blood-brain barrier (26,27), thus affecting regional metabolism and microcirculation (4). Chronic hyperglycemia, which further alters membrane permeability (26,27) and decreases regional blood flow, may lead to permanent cell damage (25).…”

Section: Multiple Regression Analysismentioning

confidence: 99%

Cerebral Blood Flow Velocity and Periventricular White Matter Hyperintensities in Type 2 Diabetes

Novak

Alsop²,

Abduljalil³

et al. 2006

Diabetes Care

147

101

View full text Add to dashboard Cite

OBJECTIVE -Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs.RESEARCH DESIGN AND METHODS -We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 Ϯ 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO 2 rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI.RESULTS -The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo-and hypercapnia (P Ͻ 0.0001), and impaired CO 2 reactivity (P ϭ 0.05). WMH volume was negatively correlated with baseline BFV (P Ͻ 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA 1c (A1C), and inflammatory markers and positively associated with systolic blood pressure (R 2 ϭ 0.86, P Ͻ 0.0001).CONCLUSIONS -Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.

show abstract

Cerebrovascular and Brain Microanatomy in Spontaneously Hypertensive Rats with Streptozotocin‐Induced Diabetes

Cited by 18 publications

References 50 publications

Cerebrovascular Complications of Diabetes: Focus on Stroke

Cerebrovascular Complications of Diabetes: Focus on Stroke

Animal models of attention-deficit hyperactivity disorder

Cerebral Blood Flow Velocity and Periventricular White Matter Hyperintensities in Type 2 Diabetes

Contact Info

Product

Resources

About