The Sleeping Brain
Hanno W. Kirk in Restoring the Brain, 2020
Research into brain activity during sleep has demonstrated that the so-called glymphatic system of the brain, analogous to the systemic lymphatic system of the body, probably acts as a conduit for flushing toxins from neurons into the general circulation. Putative neurotoxins, such as beta amyloid, alpha synuclein and tau, accumulate within the interstitium (ISF) of the CNS during consciousness. The ISF is in dynamic equilibrium with the cerebrospinal fluid (CSF), resulting in convective exchange between the two fluid compartments. The channels of the ISF, referred to as the glymphatic system, envelop the neurons, glia and cerebral vasculature with CSF influxing from the arterial side and ISF into the venules. During sleep, the volume of the glymphatic system increases by approximately 60% compared to waking, which allows for enhanced clearance of the aforementioned neurotoxins.13 The increase in clearance from this effective volume expansion is 95% compared to waking clearance. It may also be involved in neutralizing the soporific effects of adenosine that accumulates during consciousness.
The Crucial Role of Craniofacial Growth on Airway, Sleep, and the Temporomandibular Joint
Aruna Bakhru in Nutrition and Integrative Medicine, 2018
Recently, the University of Virginia Department of Neuroscience discovered that the brain has a series of lymphatic vessels directly linking the brain to the immune system. This changes entirely the way we perceive the neuroimmune interaction. It appears the lymphatic system functions as a second step in the drainage of fluid from the brain after plasma proteins and other cellular debris are drained into the CSF through the glymphatic system and then back into the bloodstream along deep cervical lymph nodes. This new discovery directly links the brain's lymphatic system with the peripheral immune system.
Outdoor Air Pollution
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Regardless of the route, its solutes and proteins ultimately reach the liver, where they are degraded. As such, the glymphatic system, so named for its dependence on glial water channels and its adoption of a clearance function similar to that of the peripheral lymphatic system, avoids the need for local protein processing and degradation. Instead, it facilitates transport to the same central excretion and recycling sites used by other peripheral tissues.
Beyond the amyloid hypothesis: how current research implicates autoimmunity in Alzheimer’s disease pathogenesis
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Miyo K. Chatanaka, Dorsa Sohaei, Eleftherios P. Diamandis, Ioannis Prassas
The brain is a highly metabolic organ that accounts for 2% of human mass and 25% of glucose use [150]. When its soluble waste products are released into the brain’s interstitial spaces, where the interstitial fluid (ISF) resides, they are transported out of the CNS for degradation. The waste’s clearance happens through a CSF-ISF solute exchange, and this is facilitated by aquaporin 4 (AQP4) channels that decrease the resistance between the parenchymal perivascular and interstitial spaces [151]. Understanding the intricacies of solute drainage through the help of astrocytic AQP4 channels led to the naming of the pathway: glial-associated lymphatic system, or glymphatic system [151]. The glymphatic system, therefore, is a CNS-specific clearance system that allows for waste from the ISF to be drained out of the brain [152].
Influence of hemodynamics on enlarged perivascular spaces in atherosclerotic large vessel disease
Published in Neurological Research, 2018
Takeshi Mikami, Tomoaki Tamada, Hime Suzuki, Ryo Ukai, Masahiko Wanibuchi, Nobuhiro Mikuni
The perivascular space consists of gaps containing cerebrospinal fluid (CSF), and it surrounds small blood vessels penetrating the brain parenchyma [1]. This space provides a perivascular lymphatic drainage pathway for the removal of interstitial fluid and solutes including amyloid beta from the brain parenchyma [17,18]. This system plays an important role in the inflammatory and immunological responses of the brain and is known as the glymphatic system. A variety of neurological disorders disturb the balance of interstitial fluid and solutes in the central nervous system either secondary to the generation of excess interstitial fluid or the failure of the perivascular drainage pathways [17]. The pathophysiology related to the accumulation of interstitial fluid and solutes in the perivascular space remains unknown. In this study, we compared the EPVS in patients diagnosed with atherosclerotic large vessel disease with and without hemodynamic compromise or stroke. Additionally, we studied the pathophysiology of EPVS in large vessel disease.
Deciphering Alzheimer’s disease: predicting new therapeutic strategies via improved understanding of biology and pathogenesis
Published in Expert Opinion on Therapeutic Targets, 2020
Rita Khoury, George T. Grossberg
The glymphatic system has recently emerged as a new system of drug delivery to the brain that bypasses the BBB ‘gatekeeper’ of the CNS and decreased the risk of toxic peripheral side effects. For instance, insulin-like growth factor-1 (IGF-1) is a neuroprotective molecule that is associated with increased risk of carcinogenesis when administered peripherally. The ependymal route directly delivers IGF-1 to the brain at optimal concentrations and prevents any peripheral toxicity [62]. Additionally, AQP4 water channels is another therapeutic target within the glymphatic pathway. Unfortunately, no specific drug has yet been developed to target this molecule due to its poor druggability. AQP4 polarization at the astrocytic end-feet is however regulated by adenosine.Hence, developing selective blockers of Adenosine 2A receptors seems to be an interesting treatment strategy for AD [77].
Related Knowledge Centers
- Central Nervous System
- Cerebrospinal Fluid
- Parenchyma
- Protein
- Sleep
- Spinal Cord
- Brain
- Solution
- Pulse
- Aquaporin-4