Brain inflammation and neurodegenerative diseases. Can MLD prevent progression?

Cerebral spinal fluid (CFS) is sometimes referred to as a 3rd circulation system, functioning as the lymphatic equivalent to clear wastes from the brain and spinal cord (CNS). By the second half of the 20th century we knew that; while there were no lymph vessels as we would recognise them inside the CNS, the lymph obligatory load (LOL) was not 100% resorbed in the venous sinuses as had been believed before that.

Diagram of lymph vessels draining the CNS, showing the dense collection of initial vessels associated with the olfactory route.

It is well established that most of the LOL (water, macromolecules, cells, cytokines, metabolic wastes and antigens) makes its way via the subarachnoid sheath to the perineurium of the cranial and spinal nerves, and the perivascular basement membrane of the cerebral blood vessels. The bulk of the fluid volume exits through the cribriform plate along the olfactory nerve route and once outside the CNS is picked up by the dense initial lymph plexus of the nasopharyngeal lymphatics for transport to the deep cervical lymphatic nodes (1).

21st Century research is revealing the molecular mechanisms and pathways involved in moving the LOL from the brain tissue toward these CNS exits. This includes specialised lymphatic glial cells and recognition of a ‘glymphatic system’. The route these cells and molecules take within the brain involve the basement membrane of the blood vessels where we find glymph travelling along paravasular sinuses toward the meningeal and perineural lymphatic network. Like all body systems the CNS drainage system is affected by aging and genetics, with some interesting observations on the influence of sleep-wake cycles and body posture (which makes me worry about the people I know who can’t sleep flat).

Research on mice indicates that waste removal occurs more efficiently during sleep, and rats sleeping flat on their sides had better elimination of metabolic wastes than rats with their heads in a more upright position. Wix stock image.

Lymphatic drainage of the CNS is also influenced by pathological conditions or diseases such as stroke, Alzheimer’s, brain tumours, neuroinflammation, and oedema caused by traumatic brain injury. In a which-came-first scenario, impairment of the brain lymphatic system is a factor in age-related cognitive changes and pathogenesis of the same list of neurological conditions and diseases, and it is now well accepted that CNS lymphatic drainage is implicated in the generation and progression of many CNS pathologies (2). Neuroinflammation is also emerging as an important factor in disease initiation and progression and is now under investigation in an array of mental health conditions including depression (the biggest cause of disability globally).

Dr Vodder's Textbook of MLD, Volume I (superseded)

All of which confirms for me that MLD to stimulate the nasopharyngeal lymphatics is still the best way remove cerebral oedema after stroke or traumatic brain injury and has the potential to help slow, or perhaps even prevent, many neurological conditions.

And like all chronic conditions the earlier we start regular MLD the better, I'm sure it is easier to keep clearing the Ab molecules as they are generated in the brain, than to remove them once they have formed amyloid plaques.

I would also recommend preventative MLD for people who have an identified genetic risk of any neurodegenerative condition.

Significance research is underway on improving brain lymphatic drainage in neurodegenerative, neurovascular and neuroinflammatory diseases. It will be primarily geared towards developing drug or genetic therapies to either boost the glymphatic system, or to find ways to use the olfactory lymph drainage route to bypass the blood brain barrier, but it will also further our understanding of the complex and fascinating lymphatic system as a whole, and I can’t wait to read about the next exciting discovery.

In the meantime, I feel reassured that what I am teaching in Applied MLD for cerebral oedema is going to be of enormous benefit in a whole range of neural conditions. And just as it has never failed to amaze me how the Vodder’s developed their precise technique for applying optimal shearing forces into the skin and tissue several decades before Mislin described the stretch-receptor-reflex, I am now in awe of how their focus on the olfactory and CNS pathways in neurological treatments has preceded these new discoveries on the importance of lymphatic drainage in brain health and disease.

1: Sun, B.L. et al Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

Prog Neurobiol 2018, 163-164, 118-143, doi:10.1016/j.pneurobio.2017.08.007.

2: Chen, J., et al. (2021). The lymphatic drainage system of the CNS plays a role in lymphatic drainage, immunity, and neuroinflammation in stroke.

J Leukoc Biol. 2021/04/23 doi:10.1016/j.pneurobio.2017.08.007