![]() All components of the BBB can be affected by ischemia, including endothelial cells, astrocytes, pericytes, tight-junctions, and the extracellular matrix. Multiple changes at the BBB have been found in stroke, such as inflammation, decreased TJs protein expression, and extended transendothelial permeability. During ischemic stroke, the BBB is disrupted, leading to vasogenic edema formation and hemorrhagic transformation. The BBB plays a crucial role in maintaining the homeostatic microenvironment of the CNS and protecting the brain tissue from exposure to potentially toxic substances. JAMs interact with intracellular scaffold proteins, such as zonula occludens (ZO)-1, ZO-2, and ZO-3, which are anchored to actin and the cytoskeleton via cingulin dimers. Play an important role in maintaining the integrity of TJs: claudins, occludins, and junctional adhesion molecules (JAMs). TJs provide asymmetrical distribution of the apical and basolateral cell membranes of the endothelia and assist in controlling the paracellular permeability across the BBB. The formation of very closed TJs between cerebral ECs comprises the unique barrier properties of the BBB. Together with pericytes, astrocytes, microglia and the surrounding basement membrane, the BBB forms a selective physical barrier that separates the bloodstream from the brain parenchyma. The blood-brain barrier is formed by a continuous layer of non-fenestrated endothelial cells (ECs) connected by tight-junctions (TJs). Furthermore, numerous studies have established that neuroinflammatory mechanisms greatly contribute to blood-brain barrier (BBB) damage and disruption following ischemic stroke. Previous studies have demonstrated that targeting inflammation and immunomodulation may offer an extended window of application for stroke therapy. Currently, the only available treatment for stroke consists of thrombolytic therapy and embolectomy, which have a very limited time window. Specific regional fat depots lead to abnormal secretion of adipose factors which in turn may penetrate the blood-brain barrier leading to brain damage and to cognitive decline.Stroke is still one of the main causes of long-term disability, leading to a substantial burden to the healthcare system and economy. Regional adiposity, which is modifiable, may explain discrepancies in associations of global adiposity, brain, and cognition. Pancreatic fat was the least studied regional fat. Visceral adipose tissue (VAT) was the most studied regional fat, along with liver fat through non-alcoholic fatty liver disease (NAFLD). However, different regional fat depots can have different cognitive outcomes and affect the brain differently. Based on the currently available literature, the findings suggest that different regional fat depots are likely associated with an increased risk of cognitive impairment, brain changes, and dementia, especially AD. PubMed, PsychInfo, and web of science were used as electronic databases for literature searches until November 2022. Studies on children and adolescents, animal studies, and studies of patients with gastrointestinal diseases were excluded. We included only studies that have assessed regional adiposity using imaging technics and excluded studies that were review articles, abstract only, or letters to the editor. This systematic review included 32 studies in the English language, conducted in humans aged 18 years and over with assessment of regional adiposity, cognitive function, dementia, and brain measures. ![]() The goal of this systematic review is to explore whether regional fat depots, rather than central obesity, should be used to understand the mechanism underlying the association between adiposity and brain. Fat-specific targeted therapies could lead to personalized improvement of cognition. Regional fat distribution may contribute differently to cognitive decline and Alzheimer’s disease (AD)-related brain changes. BMI does not represent regional fat distribution which differs between sexes, race, and age. Body mass index (BMI) is the most common measure of global adiposity, but inconsistent results were found since it is a global measurement. You just subscribed to receive the final version of the articleĪdiposity has been previously associated with cognitive impairment and Alzheimer’s disease and related disorders (ADRD).
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