The Re-Mind treatment is based on perispinal/subcutaneous injection of Etanercept over the cervical spine. A proposed pathway then leads through the external vertebral venous plexus and Batson’s valveless venous network to the spinal canal and dural venous sinuses. Treatment is combined with the Trendelenburg position to promote retrograde venous flow towards the skull and central nervous system (CNS).
In conditions including stroke, traumatic brain injury (TBI), and concussion, the blood–brain barrier may become more permeable. This may make it easier for a large biological molecule such as Etanercept, a TNF-α receptor fusion protein, to reach inflammatory areas in the CNS.
1. Vertebral venous plexus (Batson system)
This is the principal proposed transport mechanism for perispinal Etanercept. Batson’s venous plexus is a valveless venous system connecting:
- vertebral veins
- epidural veins
- intracranial venous sinuses
Because it has no venous valves, flow may reverse depending on pressure and body position.
The proposed mechanism
- Perispinal injection
- Diffusion to the vertebral venous plexus
- Retrograde transport towards the skull
- Passage to the dural venous sinuses, perivascular spaces, and potentially the cerebrospinal fluid (CSF)
This is why the Trendelenburg position is used after injection.
2. The glymphatic system
In the glymphatic system, CSF circulates along arteries, enters perivascular spaces, passes through the brain interstitium, and exits along veins. The system is driven in part by Aquaporin-4 on astrocytes.
Once a molecule reaches the CSF or perivascular spaces, glymphatic flow may distribute it through the brain. Sleep, inflammation, and trauma can alter this transport. In TBI and concussion, glymphatic changes are thought to contribute to persistent neuroinflammation.
3. Meningeal lymphatic vessels
True meningeal lymphatic vessels were identified in the dura mater in 2015. They drain CSF and immune cells, run alongside the dural sinuses, and connect to cervical lymph nodes.
They play an important role in CNS immunology. It has been proposed that perivascular connections could also provide an entry route for biological molecules such as Etanercept.
4. Blood–brain barrier permeability
Even mild TBI or concussion, stroke, and haemorrhage can cause microvascular damage, endothelial dysfunction, and changes to the tight junctions of the blood–brain barrier.
Inflammatory mediators such as TNF-α, IL-1β, and reactive oxygen species (ROS) may downregulate claudin-5 and occludin and increase paracellular permeability, leaving the blood–brain barrier more permeable in focal areas.
5. Blood-flow regulation and TNF-α
The relationship between disturbed circulation and elevated TNF-α in cerebrospinal fluid is central to neuroinflammation associated with ischaemic and traumatic brain injury.
- Blood–brain barrier dysfunction: Elevated TNF-α may activate inflammatory signalling, increase barrier permeability, and contribute to fluid leakage, oedema, and haemodynamic instability.
- Neuroinflammation and excitotoxicity: TNF-α links neuroinflammation with excitotoxicity and may indirectly affect local blood flow and contribute to cell and tissue injury.
Blood–brain barrier dysfunction is described as a possible factor allowing large proteins such as TNF-α inhibitors to reach the CNS.
Source: RN Klinik: Etanercept’s pathway and mechanism of action in the CNS. This article describes proposed biological mechanisms and is not personal medical advice.
