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Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury
AbstractSpreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain ’s gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue’s energy st atus, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spreading depo...
Source: AGE - December 8, 2019 Category: Geriatrics Source Type: research

Transforming growth factor- β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke
AbstractAging and stroke alter the composition of the basement membrane and reduce the perivascular distribution of cerebrospinal fluid and solutes, which may contribute to poor functional recovery in elderly patients. Following stroke, TGF- β induces astrocyte activation and subsequent glial scar development. This is dysregulated with aging and could lead to chronic, detrimental changes within the basement membrane. We hypothesized that TGF-β induces basement membrane fibrosis after stroke, leading to impaired perivascular CSF distri bution and poor functional recovery in aged animals. We found that CSF entered the aged...
Source: AGE - November 12, 2019 Category: Geriatrics Source Type: research

Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys
AbstractCortical injury, such as injuries after stroke or age-related ischemic events, triggers a cascade of degeneration accompanied by inflammatory responses that mediate neurological deficits. Therapeutics that modulate such neuroinflammatory responses in the aging brain have the potential to reduce neurological dysfunction and promote recovery. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) are lipid-bound, nanoscale vesicles that can modulate inflammation and enhance recovery in rodent stroke models. We recently assessed the efficacy of intravenous infusions of MSC-EVs (24-h and 14-days post-injury) a...
Source: AGE - November 5, 2019 Category: Geriatrics Source Type: research

Gastro-intestinal and oral microbiome signatures associated with healthy aging
AbstractThe human oral and gut microbiomes influence health via competition for a distinct niche in the body with pathogens, via metabolic capabilities that increase host digestive capacity and generate compounds engaged in signaling pathways and modulation of immune system functions. Old age alters our metabolic and regenerative capacity. Following recruitment of 65 human subjects in the age range of 70 to 82, we discerned healthy aging (HA) and non-healthy aging (NHA) cohorts discordant in the occurrence of one or more major diseases: (1) cancer, (2) acute or chronic cardiovascular diseases, (3) acute or chronic pulmonar...
Source: AGE - October 15, 2019 Category: Geriatrics Source Type: research

Genetic conversion of proliferative astroglia into neurons after cerebral ischemia: a new therapeutic tool for the aged brain?
AbstractIschemic stroke represents the 2nd leading cause of death worldwide and the leading cause for long-term disabilities, for which no cure exists. After stroke, neurons are frequently lost in the infarct core. On the other hand, other cells such as astrocytes become reactive and proliferative, disrupting the neurovascular unit in the lesioned area, especially in the aged brain. Therefore, restoring the balance between neurons and nonneuronal cells within the perilesional area is crucial for post stroke recovery. In addition, the aged post stroke brain mounts a fulminant proliferative astroglial response leading to the...
Source: AGE - July 11, 2019 Category: Geriatrics Source Type: research

Genomic instability and innate immune responses to self-DNA in progeria
AbstractIn the last decade, we have seen increasing evidence of the importance of structural nuclear proteins such as lamins in nuclear architecture and compartmentalization of genome function and in the maintenance of mechanical stability and genome integrity. With over 400 mutations identified in theLMNA gene (encoding for A-type lamins) associated with more than ten distinct degenerative disorders, the role of lamins as genome caretakers and the contribution of lamins dysfunction to disease are unarguable. However, the molecular mechanisms whereby lamins mutations cause pathologies remain less understood. Here, we revie...
Source: AGE - July 5, 2019 Category: Geriatrics Source Type: research

Systemic milieu and age-related deterioration
AbstractAging is a fundamental biological process accompanied by a general decline in tissue function and an increased risk for age-related disease. The risk for cardiovascular, stroke, cancer, and neurodegenerative diseases significantly increases with aging, especially in people aged 60  years and older in the USA. Although the cellular and molecular mechanisms underlying aging and age-related disease are beginning to be unraveled, the role of the systemic milieu remains unknown. Recent studies have shown that systemic factors in young blood can revise age-related impairments and extend organismal lifespan, suggesting t...
Source: AGE - May 30, 2019 Category: Geriatrics Source Type: research

Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia
We report here that genetic knockout (KO) of MLCK210 protects against cerebral microhemorrhages and neuroinflammation induced by chronic dietary hyperhomocysteinemia. Overall, the results are consistent with an accumulating body of evidence supporting MLCK210 as a potential therapeutic target for tissue barrier dysfunction and specifically implicate it in BBB dysfunction and neuroinflammation in a model of VCID.
Source: AGE - May 18, 2019 Category: Geriatrics Source Type: research

The association between relevant comorbidities and dementia in patients with atrial fibrillation
AbstractRisk of dementia is increased in patients with atrial fibrillation (AF). We aimed to  study associations between relevant comorbidities and prevalent as well as incident dementia in AF patients. Study population included all adults (n = 12,283) ≥ 45 years diagnosed with AF at 75 primary care centers in Sweden 2001–2007. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (95% CI) for associations between comorbidities and prevalent dementia. In a subsample (n = 12,096), (excluding patients with dementia diagnosed before AF onset), Cox regression was used to esti...
Source: AGE - June 22, 2018 Category: Geriatrics Source Type: research

Prostanoid-mediated contractions of the carotid artery become Nox2-independent with aging
In conclusion, aging decreases prostanoid-mediated contractility in the carotid artery involving a loss of Nox2 activity and is associated with impaired endothelium-dependent, NO-mediated relaxation. These findings may contribute to a better understanding of the pathophysiology of carotid artery disease and the aging process.
Source: AGE - July 31, 2015 Category: Geriatrics Source Type: research

Fatiguing exercise initiated later in life reduces incidence of fibrillation and improves sleep quality in Drosophila
This study aimed to investigate whether exercise training started later in life is beneficial to cardiac aging in Drosophila. We examined 4-week-old wild-type virgin female flies that were exposed to exercise periods of either 1.5, 2.0, or 2.5 h per day, 5 days a week for 2 weeks. Using M-mode traces to analyze cardiac function by looking at parameters including heart rate, rhythmicity, systolic and diastolic diameter, and interval and fractional shortening, we found that cardiac function declined with age, shown by an increase in the number of fibrillation events and a decrease in fractional shortening. About 2.0 and 2...
Source: AGE - July 24, 2015 Category: Geriatrics Source Type: research

Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model
Abstract Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3- and 18-month-old male Sprague–Dawley rats. The adhesion molecules E- and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (G...
Source: AGE - September 3, 2014 Category: Geriatrics Source Type: research

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