Waste clearance shapes aging brain health

 Your competent? doctor has known of this brain waste removal problem a long time. Was anything done? Obviously not since no protocols exist to address the problem, why not? If I, not medically trained can see what needs to be done, why are our stroke medical 'professionals' so fucking incompetent?

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

brain waste removal (11 posts to February 2018)

Waste clearance shapes aging brain health

Li-Feng Jiang-Xie^1,2,4 ∙ Antoine Drieu^3,4 ∙ Jonathan Kipnis^1,2 kipnis@wustl.edu

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Summary

Brain health is intimately connected to fluid flow dynamics that cleanse the brain of potentially harmful waste material. This system is regulated by vascular dynamics, the maintenance of perivascular spaces, neural activity during sleep, and lymphatic drainage in the meningeal layers. However, aging can impinge on each of these layers of regulation, leading to impaired brain cleansing and the emergence of various age-associated neurological disorders, including Alzheimer’s and Parkinson’s diseases. Understanding the intricacies of fluid flow regulation in the brain and how this becomes altered with age could reveal new targets and therapeutic strategies to tackle age-associated neurological decline.

Keywords

1. neuroimmunology
2. meningeal immunity
3. brain borders
4. sleep
5. brain clearance
6. lymphatic
7. meningeal lymphatic

Introduction

The global population is aging, and the United Nations estimates that one in six people will be aged over 65 by 2050. Cerebrovascular diseases are major causes of mortality and morbidity, and their prevalence increases with age. For example, vascular cognitive impairments and dementia are the leading causes of disability in aged individuals.^1,2 Additionally, evidence suggests that brain waste clearance through vascular network decreases with age, contributing to the development of neurodegenerative diseases.³ Thus, understanding how the brain vasculature and associated fluid flow are altered during aging could have substantial implications for the development and treatment of a variety of neurological diseases.

In recent years, our understanding of brain fluid dynamics has been greatly enriched, unveiling a complex network of flows that are essential for maintaining brain homeostasis. These flows are particularly important for preventing the buildup of potentially harmful substances that can affect brain health. The brain’s waste clearance system (a concept also known as glymphatic system^4,5) is composed of peri-arterial, parenchymal, and peri-venous flows (Figure 1). Peri-arterial flow occurs within the perivascular spaces of the brain and is primarily driven by arterial pulsation and changes in local blood pressure. Parenchymal border macrophages (PBMs) are specialized macrophages that play a crucial role in degrading the extracellular matrix (ECM) within these spaces, ensuring that cerebrospinal fluid (CSF) can flow unimpeded along the arteries.⁶ However, the efficiency of these vascular dynamics can decline with age, leading to impaired fluid flow.^3,6

Figure 1 Major anatomical pathways for brain cleansing

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Within the brain parenchyma, synchronized neural activity, especially during sleep, is a key regulator of fluid movement through the dense brain tissue. This process is most effective during slow-wave sleep, during which large-scale, rhythmic neural oscillations create the necessary driving force to propel interstitial fluid and facilitate the clearance of metabolic waste products into the CSF.^7,8,9,10 The coupling of neural activity with fluid flow not only highlights the importance of sleep for brain health but also suggests that sleep disruptions that increase with age can have profound effects on the brain’s waste clearance capabilities.

The peri-venous flow carrying waste materials ultimately reaches the meningeal lymphatic vessels, which drain CSF from the brain to the cervical lymph nodes.^11,12 These lymphatic vessels undergo major structural changes with aging, including reduced vessel diameter, altered valve distribution, and increased permeability. Such changes diminish the brain’s ability to efficiently remove waste, contributing to the accumulation of toxic substances and increasing the risk of neurodegenerative diseases.^13,14,15 In general, brain waste materials include but are not limited to metabolic byproducts, oxidized lipids, and aggregation-prone peptides.^16,17,18 It is worth mentioning that the waste products derived from the brain may also serve as signaling molecules for immune cells in the meninges and skull, potentially forming dedicated channels for neuroimmune crosstalk.^19,20

Understanding these fluid flow dynamics, the underlying regulatory mechanisms, and how they change with age is crucial for developing therapeutic strategies aimed at preserving cognitive function and preventing age-related neurological decline. In this review, we discuss the different aspects of fluid flow through the brain, how these systems function in unison, and what happens when their function is altered during aging.

More at link.