The Sleep Reset: How Rest Supports Brain Health

Many of us are aware of the protective barrier of our brains from the outside world, known as the blood-brain barrier (BBB). But some of us may not be aware of the recovery apparatus of our brain that occurs during the night, which is the glymphatic system, the lymphatic system of the brain. 

The hypothesis that cerebrospinal fluid and interstitial fluid mix and enable waste clearance through the perivascular space was proposed as early as the 1870s, and the activation of this process during sleep was proposed in the 1890s. The formal discussion of the glymphatic system in research is relatively new. The first mention of the brain’s glymphatic system was in 2012, where it was described as a para-vascular pathway that facilitates the cerebrospinal fluid (CSF) through the brain. Since its elucidation in 2012, the glymphatic system has provoked controversy, primarily because of a lack of data and adequate tools to characterize non-invasively a low-pressure fluid transport system residing in an electrically active organ encased within the rigid walls of the skull. 

So, how is the lymphatic system different in the brain than the rest of the body? The brain is one of the most energetically demanding organs within the body, but we have the blood-brain barrier protecting our brain. The blood–brain barrier limits the influx of plasma ultrafiltrate from the microvascular bed, which in peripheral tissue drives waste clearance. The brain tissue also lacks traditional lymphatic capillaries to establish directional fluid movement and waste clearance. Instead, the brain uses a network termed the glymphatic system to support a constant influx of cerebrospinal fluid (CSF) that drives the export of metabolic waste. 

The glymphatic system is a network of tunnel-like perivascular spaces that promotes directional, bulk fluid movement through the brain. Glymphatic flow consists of CSF entering the periarterial spaces of the brain, penetrating into the tissue and mixing with interstitial fluid (ISF), and ultimately carrying solutes to the perivenous space to exit the brain tissue. 

Perivascular spaces are fluid-containing channels that run alongside the vasculature, enclosed by the vascular endfeet of astrocytes. The brain vasculature comprises endothelial cells surrounded by smooth muscle cells or pericytes. Astrocytes, the glial cells within the brain, cover the vasculature with their specialized endfeet processes. These astrocytic endfeet delineate the perivascular space from the brain tissue, creating tunnel-like structures that enable fast fluid flow. 

A key perspective that has emerged since the initial description of the glymphatic system is that while this biology is dependent on microscopic features, such as perivascular spaces, astroglial endfeet, and meningeal lymphatic vessels, it functions at the macroscopic scale of the cranium, cerebrovascular network, CSF circulation, brain, and spinal cord. This understanding of the glymphatic potentially leads to the development of clinical applications concerning drug delivery, stroke, cardiac arrest, and neurodegenerative disorders like Alzheimer’s disease, while we sleep.  

Glymphatic system and sleep 

Most organisms have a sleep-like state in which the brain shows fundamentally different activity patterns and sensory processing compared with the “awake state”. Yet, the neurobiological purpose of sleep has long eluded scientists. The activation of glymphatic fluid transport during sleep might provide an answer. The brain has very characteristic electrical activity during sleep. Broadly speaking, sleep contains both rapid eye movement (REM) sleep and non-REM (NREM) sleep. REM sleep is characterized by a more complex type of synapses, which is promoted by active fluid transport, which would compromise the precision of brain circuit function needed for higher information processing. Norepinephrine, a neurotransmitter that promotes wakefulness, inhibits glymphatic flow, supporting this hypothesis. 

It is believed that glymphatic system is “on” during sleep to provide the essential housekeeping function of exporting metabolic waste, but also “off” during wakefulness to avoid spillover of the excitatory neurotransmitter glutamate outside of the synapse. On top of that, the glymphatic system shows evidence of being regulated by a 24-hour circadian timing. 

Another aspect to consider is that the glymphatic does decline with natural aging and after brain injury, so it would be wise to practice a regimen that restores the proper function during sleep as we age. 

It has been shown that astrocytes are involved in both homeostatic and circadian regulation of the sleep process and can be considered as a potential therapeutic target for sleep disorders. 

Ayurveda and sleep 

Nidra (sleep) is regarded as one of the Trayopastambha (three essential pillars of life) in Ayurveda, contributing significantly to physical, mental, and spiritual well-being. Swapna (dreams), an integral phenomenon occurring during Nidra, is interpreted in Ayurvedic texts as reflective of the Manas (mind), Dosha predominance, and psychological states. In contemporary sleep science, sleep and dreams are analyzed through neurophysiological, hormonal, and cognitive frameworks. A comparative holistic understanding of these concepts may offer insights into managing sleep disorders and promoting optimal health. 

Since sleep can be associated with neurodegeneration as we age, Ayurveda considers neurodegenerative conditions to be brought by the imbalance of “Vata”, the energy that moves through the brain and the nerves. The scholars behind classical ayurvedic literature considered neural impulses to be a kind of air traveling through the body, controlling both voluntary and involuntary functions. Oxygen is the real-time mediator of the homeostatic signaling system, and defective oxygen transport. Indicating that impairment in oxygenation is the principal underlying factor in neurodegenerative conditions. 

Saffron’s and Ashwagandha's effect on sleep  

Saffron (Crocus sativus) has been shown to be effective in balancing mood, but its effect on sleep quality has only been recently investigated. Since saffron can modulate brain GABA (gamma-aminobutyric acid) and serotonin levels, which are known to decrease in those with insomnia, it suggests the likelihood of saffron supporting sleep. A randomized double-blind controlled study was conducted with 66 subjects presenting mild to moderate sleep disorder associated with anxiety. Those who received 15.5 mg of a saffron extract per day for six weeks (22 participants) supported the ability to sleep. The Leeds Sleep Evaluation Questionnaire (LSEQ) was also used, and improved sleep quality, sleep latency, and sleep duration were reported. 

It is also known that low blood oxygen, hypoxemia, can lead to insomnia and sleeping disorders, which can prime the brain to neurodegenerative conditions. In Ayurveda medicine, there are therapeutic approaches used in neurodegenerative conditions that suggest a similar mechanism of action to manage hypoxic insomnia by enhancing oxygenation. Withania somnifera is known to alter the oxidative stress markers of the body. This property is found to support nerve health, free radical scavenging activity, significantly reduce lipid peroxidation, increase the superoxide dismutase (SOD), and catalase activities. As you can see, all of this evidence-based research has supported Ashwagandha’s thousands of years of use in Ayurvedic medicinal systems for supporting neuronal health. The synergistic effects produced by Ashwagandha suggest it has a profound mechanism of enhancement of oxygenation.  

This suggests that enhancing oxygenation improves homeostatic regulation. The involvement of the glymphatic system in neurodegenerative conditions is very prominent. Enhancement of oxygenation can activate glymphatic clearance pathways and can produce multiple target actions that have promising effects in delaying the progression of neurodegeneration and instead promote neurogenesis. Through enhancement of oxygenation, the disruptions in homeostatic mechanisms governing life can be re-established, which can induce healing and can be used to preserve health. 

Practical Application to support the Glymph through breathing 

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