It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via ...the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood-brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood-brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.
Aging is associated with a progressive loss of function in all organs. Under normal conditions the physiologic compensation for age-related deficits is sufficient, but during times of stress the ...limitations of this reserve become evident. Explanations for this reduction in reserve include the changes in the microcirculation that occur during the normal aging process. The microcirculation is defined as the blood flow through arterioles, capillaries and venules, which are the smallest vessels in the vasculature and are embedded within organs and tissues. Optimal strategies to maintain the microvasculature following surgery and other stressors must use multifactorial approaches. Using skin as the model organ, we will review the anatomical and functional changes in the microcirculation with aging, and some of the available clinical strategies to potentially mitigate the effect of these changes on important clinical outcomes.
•Age related changes in the microcirculation lead to reduced reserve during stress.•Age related changes include decreased density, lack of organization and impaired reactivity.•Current approaches to improve the microcirculation focus on optimizing vascular reactivity.•Future directions will need a multifactorial approach to improve microvascular function.
Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, ...but many mechanistic questions remain.
We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using (14)C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to (14)C-sucrose and radioactive albumin.
In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with (14)C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and (14)C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes.
The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is to be dependent on COX but not on oxidative stress. Based on in vivo and in vitro measures of neuroinflammation, it appears that astrocytes, microglia/macrophages, and pericytes play little role in the LPS-mediated disruption of the BBB.
Age-related changes in skin contribute to impaired wound healing after surgical procedures. Changes in skin with age include decline in thickness and composition, a decrease in the number of most ...cell types, and diminished microcirculation. The microcirculation provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin. Perioperative management can be modified to minimize insults to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension are examples of adjustable variables that support the microcirculation. Anesthetic agents influence the microcirculation of a combination of effects on cardiac output, arterial pressure, and local microvascular changes. The authors examined the role of anesthetic management in optimizing the microcirculation and potentially improving postoperative wound repair in older persons.
The blood-brain barrier (BBB) protects the central nervous system (CNS) from unregulated exposure to the blood and its contents. The BBB also controls the blood-to-brain and brain-to-blood permeation ...of many substances, resulting in nourishment of the CNS, its homeostatic regulation and communication between the CNS and peripheral tissues. The cells forming the BBB communicate with cells of the brain and in the periphery. This highly regulated interface changes with healthy aging. Here, we review those changes, starting with morphology and disruption. Transporter changes include those for amyloid beta peptide, glucose and drugs. Brain fluid dynamics, pericyte health and basement membrane and glycocalyx compositions are all altered with healthy aging. Carrying the
allele leads to an acceleration of most of the BBB's age-related changes. We discuss how alterations in the BBB that occur with healthy aging reflect adaptation to the postreproductive phase of life and may affect vulnerability to age-associated diseases.
There is increasing interest in defining the location, content, and role of extracellular matrix (ECM) components in brain structure and function during development, aging, injury, and ...neurodegeneration. Studies in vivo confirm brain ECM has a dynamic composition with constitutive and induced alterations that impact subsequent cell-cell and cell-matrix interactions. Moreover, it is clear that for any given ECM component, the brain region, and cell type within that location, determines the direction, magnitude, and composition of those changes. This review will examine the ECM at the neurovascular unit (NVU) and the blood-brain barrier (BBB) within the NVU. The discussion will begin at the glycocalyx ECM on the luminal surface of the vasculature, and progress to the abluminal side with a focus on changes in basement membrane ECM during aging and neurodegeneration.
The Brain and Spinal Microvasculature in Normal Aging Khaing, Zin Z; Chandrasekaran, Abarajithan; Katta, Anjali ...
The journals of gerontology. Series A, Biological sciences and medical sciences,
08/2023, Letnik:
78, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Abstract
Changes in the brain and spinal cord microvasculature during normal aging contribute to the “sensitive” nature of aged central nervous system tissue to ischemic insults. In this review, we ...will examine alterations in the central nervous system microvasculature during normal aging, which we define as aging without a dominant pathology such as neurodegenerative processes, vascular injury or disease, or trauma. We will also discuss newer technologies to improve the study of central nervous system microvascular structure and function. Microvasculature within the brain and spinal cord will be discussed separately as anatomy and physiology differ between these compartments. Lastly, we will identify critical areas for future studies as well as key unanswered questions.
Older adults are disproportionately affected by trauma and accounted for 47% of trauma fatalities in 2016. In many populations and disease processes, described risk factors for poor clinical outcomes ...include sarcopenia and brain atrophy, but these remain to be fully characterized in older trauma patients. Sarcopenia and brain atrophy may be opportunistically evaluated via head computed tomography, which is often performed during the initial trauma evaluation.
To investigate the association of masseter sarcopenia and brain atrophy with 1-year mortality among trauma patients older than 65 years by using opportunistic computed tomography imaging.
This retrospective cohort study was conducted in a level 1 trauma center from January 1, 2011, to December 31, 2014, with a 1-year follow-up to assess mortality. Washington state residents 65 years or older who were admitted to the trauma intensive care unit with a head Abbreviated Injury Scale score of less than 3 were eligible. Patients with incomplete data and death within 1 day of admission were excluded. Data analysis was completed from June 2017 to October 2018.
Masseter muscle cross-sectional area and brain atrophy index were measured using a standard clinical Picture Archiving and Communication System application to assess for sarcopenia and brain atrophy, respectively.
Primary outcome was 1-year mortality. Secondary outcomes were discharge disposition and 30-day mortality.
The study cohort included 327 patients; 72 (22.0%) had sarcopenia only, 71 (21.7%) had brain atrophy only, 92 (28.1%) had both, and 92 (28.1%) had neither. The mean (SD) age was 77.8 (8.6) years, and 159 patients (48.6%) were women. After adjustment for age, comorbidity, complications, and injury characteristics, masseter sarcopenia and brain atrophy were both independently and cumulatively associated with mortality (masseter muscle cross-sectional area per SD less than the mean: hazard ratio, 2.0 95% CI, 1.2-3.1; P = .005; brain atrophy index per SD greater than the mean: hazard ratio, 2.0 95% CI, 1.1-3.5; P = .02).
Masseter muscle sarcopenia and brain atrophy were independently and cumulatively associated with 1-year mortality in older trauma patients after adjustment for other clinical factors. These radiologic indicators are easily measured opportunistically through standard imaging software. The results can potentially guide conversations regarding prognosis and interventions with patients and their families.
The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound ...healing slows with age. However, the basic biology underlying chronic wounds and the influence of age‐associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi‐morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age‐associated changes in chronic wound healing.
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