Threads: @braininflammationcollab
“The SARS-CoV-2 spike protein was recently found to localize in an unusual place outside the brain.
This localization pattern might explain the neuroinflammatory symptoms experienced during:
- SARS-CoV-2 infection
- Long COVID..🧵”
https://www.cell.com/cms/10.1016/j.chom.2024.11.007/attachment/4209ecf1-b91e-432d-9707-b69faa6dd986/mmc4.mp4
“Researchers from Ludwig-Maximilians-University Munich, Munich, Germany found that the SARS-CoV-2 spike protein localizes to the skull's bone marrow.
To understand why this discovery is important in the context of Long COVID we must first learn about the following:
- the meninges
- immune cells in the meninges
Read the scientific publication here:”
https://buff.ly/3DNfPGL
“\ Background - Skull Meninges Connections (SMCs):
The brain is wrapped in a 3-layer membrane called the meninges.
This protective membrane contains resident immune cells that do not come from circulation.
Instead, they traffic through specialized channels from the skull's bone marrow (to the meninges) (1).”
“But why is it important for immune cells in the meninges to come from the skull and not the blood?”
“Surprisingly, immune cells from the skull’s marrow behave differently than those from the blood. Specifically, scientists found they are (1):
- less likely to trigger autoimmunity
- less inflammatory in nature
They can also rapidly penetrate the brain following injury or inflammation (1).
Now back to the new Long COVID paper…”
“\ Results:
As we mentioned above, the spike protein was found in the skull’s bone marrow and meninges in mice.
This was associated with:
- exacerbated outcomes of stroke and traumatic brain injury
- changes in the skull-meninge physiology
- anxiety-like behavior
They also found spike protein in the skull of humans previously infected with SARS-CoV-2 but later died from non-COVID-related complications.”
“\ Results:
Further results found that injecting the spike protein directly into the skull’s bone marrow, which is outside the brain (in 🐁 ), caused pathology inside the brain such as:
- neuronal stress
- neuroinflammation”
“\ Conclusion:
This data suggests that the spike protein’s ability to accumulate in the skull’s bone marrow might be responsible for neuroinflammation (brain fog) experienced following a SARS-CoV-2 infection and in those with Long COVID.
This work also might also, “suggest a mechanism for the virus’s entry into the central nervous system “ (i.e. the skull’s bone marrow-meninge axis).”
“\ Therapeutic Implications:
The skull’s bone marrow is not behind the blood-brain barrier.
Thus, if a viable anti-neuroinflammatory target is discovered in the skull marrow, it wouldn’t need to meet the burdensome criteria of crossing the BBB.
However, more work is required to identify this putative drug candidate(s).”
“We at the Brain Inflammation Collaborative are on a mission to help scientists understand how complex neuroimmune axis conditions such as Long COVID impact our brain health and mental health.
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Literature Cited:
1. Cugurra, A., Mamuladze, T. et al. Science. Jul 23, 2021. PMID: 34083447”