scholarly journals Occult Cerebrovascular Disease and Late-Onset Epilepsy: Could Loss of Neurovascular Unit Integrity Be a Viable Model?

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Lorna M. Gibson ◽  
Stuart M. Allan ◽  
Laura M. Parkes ◽  
Hedley C. A. Emsley
Keyword(s):  
Cerebrovascular Disease ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Regional Cerebral Blood ◽  
Blood Brain Barrier Disruption ◽  
Increased Risk ◽  
Unit Function ◽  
Cerebrovascular Risk ◽  
Brain Barrier Disruption ◽  
Viable Model

Late-onset epilepsy (LOE) first occurs after 60 years of age and may be due to occult cerebrovascular disease (CVD) which confers an increased risk of stroke. However, patients with late-onset epilepsy are not currently consistently investigated or treated for cerebrovascular risk factors. We discuss how abnormalities of neurovascular unit function, namely, changes in regional cerebral blood flow and blood brain barrier disruption, may be caused by occult cerebrovascular disease but present clinically as late-onset epilepsy. We describe novel magnetic resonance imaging methods to detect abnormal neurovascular unit function in subjects with LOE and controls. We hypothesise that occult CVD may cause LOE as a result of neurovascular unit dysfunction.

scholarly journals Late-Onset Epilepsy and Occult Cerebrovascular Disease

2014 ◽  
Vol 34 (4) ◽  
pp. 564-570 ◽  
Author(s):  
Lorna M Gibson ◽  
Martha F Hanby ◽  
Sarah M Al-Bachari ◽  
Laura M Parkes ◽  
Stuart M Allan ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Late Onset ◽  
Cerebral Metabolism ◽  
Neurovascular Unit ◽  
Barrier Dysfunction ◽  
Increased Risk ◽  
Antiepileptic Drug Treatment ◽  
History Of ◽  
Ischemic Attack ◽  
The Relationship

The interface between cerebrovascular disease (CVD) and epilepsy is complex and multifaceted. Late-onset epilepsy (LOE) is increasingly common and is often attributed to CVD, and is indeed associated with an increased risk of stroke. This relationship is easily recognizable where there is a history of stroke, particularly involving the cerebral cortex. However, the relationship with otherwise occult, subcortical CVD is currently less well established yet causality is often invoked. In this review, we consider the diagnosis of LOE in clinical practice—including its behaviour as a potential mimic of acute ischemic stroke and transient ischemic attack; evidence for an association between occult CVD and LOE; and potential mechanisms of epileptogenesis in occult CVD, including potential interrelationships between disordered cerebral metabolism and perfusion, disrupted neurovascular unit integrity, blood–brain barrier dysfunction, and inflammation. We also discuss recently recognized issues concerning antiepileptic drug treatment and vascular risk and consider a variety of less common CVD entities associated with seizures.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Vol 9 (10) ◽  
pp. 262 ◽  
Author(s):  
Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Obesity, Aging, Intersects and Continuum Of Progression

2019 ◽  
Author(s):  
Melvin R. Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Functional Changes ◽  
Age Related ◽  
Increased Risk ◽  
Vascular Stiffening

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) have become parallel global pandemics and current predictions indicate they will only increase over the coming decades. These pandemics may result from the coexistent increase of obesity and aging. T2DM is associated with cognitive impairments associated with both metabolic factors, diabetic cognopathy (DC) and an increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, intersects and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. It is difficult to condense so many links between T2DM and LOAD; however, five major intersections could be considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU remodeling with resulting impaired cerebral blood flow).

scholarly journals Neurovascular Unit Alterations In The Growth Restricted Newborn Are Improved Following Ibuprofen Treatment

2021 ◽  
Author(s):  
Kirat K. Chand ◽  
Stephanie M. Miller ◽  
Gary J. Cowin ◽  
Lipsa Mohanty ◽  
Jany Pienaar ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Plasma Protein ◽  
Neurovascular Unit ◽  
Brain Parenchyma ◽  
Learning Disorders ◽  
Blood Brain Barrier Disruption ◽  
Newborn Brain ◽  
Protein Leakage ◽  
Inflammatory State ◽  
Brain Barrier Disruption

Abstract The developing brain is particularly vulnerable to fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant ranging from behavioural and learning disorders through to cerebral palsy. No treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, an anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. Using a preclinical FGR piglet model, ibuprofen was administered for three days from birth. FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident where plasma protein leakage was present, suggestive of structural deficits to the NVU. A significant increase in peripheral infiltrates were also evident in the parenchyma of FGR piglet brains. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen also attenuated plasma protein leakage, regained astrocytic end-feet interaction around vessels, and decreased T-cell infiltration into the FGR brain. These findings suggest postnatal administration of ibuprofen modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Author(s):  
Melvin Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

133Xe-DSPECT: Normalwerte von zerebraler Ruhedurchblutung und Reservekapazität

1987 ◽  
Vol 26 (05) ◽  
pp. 192-197 ◽  
Author(s):  
T. Kreisig ◽  
P. Schmiedek ◽  
G. Leinsinger ◽  
K. Einhäupl ◽  
E. Moser
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebrovascular Disease ◽  
Correlation Coefficient ◽  
Regional Cerebral Blood Flow ◽  
Regression Line ◽  
Reserve Capacity ◽  
Regional Cerebral Blood ◽  
Quantitative Measurements ◽  
Before And After

Using the 133Xe-DSPECT technique, quantitative measurements of regional cerebral blood flow (rCBF) were performed before and after provocation with acetazolamide (Diamox) i. v. in 32 patients without evidence of brain disease (normals). In 6 cases, additional studies were carried out to establish the time of maximal rCBF increase which was found to be approximately 15 min p. i. 1 g of Diamox increases the rCBF from 58 ±8 at rest to 73±5 ml/100 g/min. A Diamox dose of 2 g (9 cases) causes no further rCBF increase. After plotting the rCBF before provocation (rCBFR) and the Diamox-induced rCBF increase (reserve capacity, Δ rCBF) the regression line was Δ rCBF = −0,6 x rCBFR +50 (correlation coefficient: r = −0,77). In normals with relatively low rCBF values at rest, Diamox increases the reserve capacity much more than in normals with high rCBF values before provocation. It can be expected that this concept of measuring rCBF at rest and the reserve capacity will increase the sensitivity of distinguishing patients with reversible cerebrovascular disease (even bilateral) from normals.

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