Clearing the Mind: MLD and Glymphatic Health in an Age of Neuroinflammation

The Rising Tide of Neuroinflammatory Disease

We are living through a quiet but devastating surge in neuroinflammatory and neurodegenerative disorders. In Australia and New Zealand, Alzheimer’s disease now affects over half a million individuals, a figure projected to more than double by the year 2060 (1).

Traumatic brain injuries also disrupt thousands of lives annually, leaving those affected, and their families, to grapple with the acute and chronic consequences including persistent cerebral oedema (2).

Traditional pharmaceutical choices, while capturing immense scientific focus, often impose heavy financial burdens and carry substantial risks of severe side effects without actively reversing cognitive decline. Consequently, modern healthcare faces a critical, unmet need for non-invasive, accessible, and cost-effective therapeutic strategies designed to combat neuroinflammation and safeguard neurological longevity. To satisfy this need, clinical science has shifted its gaze toward the brain’s native waste management network: the glymphatic-lymphatic conduit (3).  

The Glymphatic System and the Brain's Drainage Highway

The central nervous system was historically viewed as entirely separate from the body’s lymphatic architecture. However, recent breakthroughs have illuminated an intricate, specialised cerebral clearing network known as the glymphatic system. We now understand that cerebral spinal fluid outflow occurs not only through traditional routes (arachnoid villi, cranial nerves, dural lymphatics) but also via perivascular spaces and microscopic cranial canals which allow bidirectional cellular trafficking, influencing immune responses and potentially contributing to chronic neuroinflammatory conditions.

Metabolic waste products and neurotoxic proteins, most notably amyloid-beta (Aβ), are actively from the brain parenchyma via the perivascular channels to be collected by meningeal lymphatic vessels and transported to the deep and superficial lymph vessels and nodes in the neck (1).  

Restriction or blockage along this critical drainage route will result in a pathological buildup of neurotoxic proteins. Secondary neuroinflammatory response will follow, accelerating neuronal cellular damage. In Alzheimer's disease, the age-related deceleration of fluid flow prevents the removal of soluble Aβ, encouraging plaque formation and widespread axonal injury.  

In acute events such as a traumatic brain injury, glymphatic clearance is significantly reduced, resulting in cytotoxic gray matter oedema, elevated intracranial pressure and severe, persistent cranial pain (2).

How Manual Lymph Drainage Accelerates Brain Clearance

Manual Lymph Drainage (MLD) is a gentle, non-invasive manual therapy which used gentle and precise manipulation of the skin and soft tissue to stimulate the intrinsic contraction of local lymphatic vessels and increase lymphatic pumping. Well researched in it's role as a core therapy in lymphoedema management, compelling new translational research demonstrates that MLD applied to the head and neck yields profound intracranial benefits (1, 3).  

In a landmark 2025 preclinical study, female 5x-FAD mice (they over express Amyloid Precursor Protein and Presenilin) underwent a twice-daily MLD protocol modelled after the clinical Vodder method. Spatial working memory and daily living activities were quantified via nest-building efficiency, and after 2 months the mice that had received MLD completely reversed these deficits back to the performance level of healthy wild-type mice (1).

(A) Representative images of nests made by WT (left image), sham treated 5x-FAD mice (middle), and MLD treated 5x-FAD mice (right). Note the incomplete nests in the 5x-FAD mice (middle) as compared to the partially restored nests in the MLD treated 5x-FAD mice (right). (B) Summary bar graph of the nest building scores show that female 5x-FAD mice build significantly incomplete nests and that these are significantly improved in 5x-FAD mice treated with MLD. Each individual data point represents one mouse. All data are represented as mean ± SEM. Statistical analysis: (B) Qualitative assessment of the nest

Biochemically, this cognitive rescue coincided with a 38% reduction in the neurotoxic Aβ42/Aβ40 ratio within the hippocampus, alongside a 33% reduction in plasma levels of neurofilament light chain (NfL), an established biomarker for neurodegeneration and axonal damage (1).

These experimental insights transfer beautifully to human clinical settings. A 2023 case study used craniocervical MLD (Leduc method) as an adjunctive therapy for a patient suffering from an acute, moderate traumatic brain injury (2).

Following six 30-minute sessions over three days, the patient experienced an incredible 66% drop in cranial pain intensity alongside a marked resolution of cerebral edema, which was objectively quantified using non-contrast CT brain scans.

MLD Techniques: Drainage of the Cerebral and Spinal Spaces

An important pathway by which CSF is removed from the cranium is movement through the cribriform plate in association with the olfactory nerves. CSF is then absorbed directly into lymphatics located in the submucosa of the olfactory epithelium. Applied MLD uses intraoral techniques to directly influence this major glymphatic drainage pathway and may have measurable benefits for neurological health, however no direct studies have yet been conducted to investigate this.

The lymph obligatory load from the central nervous system is also collected via epidural lymphatics associated with the spinal nerve exits, which can be stimulated by the MLD technique know as 'soldiers'. Additionally, with the sympathetic ganglia located alongside the vertebrae, MLD in this area also has a powerful effect on restoring autonomic balance, a vital element in all healing processes.

Conclusion

As the global burden of neuroinflammatory disease continues to escalate, the immediate deployment of low-cost, non-invasive physical therapies is paramount. Supported by compelling preclinical data demonstrating cognitive restoration, and objective human clinical evidence of oedema resolution, MLD represents a safe, effective, and immediately available intervention.

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References:

1: Bartlett, M. J., Erickson, R. P., Frye, J., Doyle, K. P., Pires, P. W., & Witte, M. H. (2025). Manual lymph drainage massage of the head and neck improves cognition and reduces pathological biomarkers in the 5x-FAD mouse model of Alzheimers disease. bioRxiv. doi:10.1101/2025.08.08.669361 https://www.biorxiv.org/content/biorxiv/early/2025/08/12/2025.08.08.669361.full.pdf

2: Esparza, W. D., Aladro-Gonzalvo, A. R., Ruíz-Hontangas, A., Celi, D., & Aguirre, M. B. (2023). The Effect of Craniofacial Manual Lymphatic Drainage after Moderate Traumatic Brain Injury. Healthcare, 11(10), 1474. Retrieved from https://www.mdpi.com/2227-9032/11/10/1474

3: Erickson, R. P., Bernas, M. J., & Witte, M. H. (2025). Manual Lymph Drainage for Alzheimer's Dementia: A Clinical Trial Whose Time Has Come? Lymphology, 58(2), 43-45. https://pubmed.ncbi.nlm.nih.gov/40803039/