Demyelination mechanisms caused by Endotoxin

Going beyond disease associations to Molecular Mechanisms requires some deep diving into huge literature and some luck.

After my presentation for WOW and AMPS in Hampton I was asked about the fact that the Australian government recognizes Transverse Myelitis as a probable Adverse Event following the AstraZeneca jab, but denies it being caused by the Pfizer jab.

Pfizer reported 249 Transverse Myelitis cases to June 2022 in its PSUR3.

Transverse Myelitis is an inflammatory Demyelation disease, where the “insulating” coating on nerve fibres is destroyed.¹ Picture credit.²

Other Substack authors have written about Demyelination and readers will find interesting material there.³ ⁴ My focus is evidence for jab Endotoxin induced effects.

Previously I covered Antiphospholipid diseases caused by Endotoxin, an very briefly mentioned Neurological damage.⁵

A clue was provided when I found a study from Israel finding that Methotrexate injections cause transient or permanent Neurological damage.⁶ This study has numerous useful references.

From a 2002 Irish study I learn that Methotrexate causes Endotoxemia via Gut Dysbiosis with confirmed elevation of blood Endotoxin.⁷

A cases report from Singapore detailed Transverse Myelitis after Methotrexate injections.⁸

Then in 2011 a Netherlands case of a Multiple Sclerosis victim who died suddenly was found on post-mortem to have Demyelination in his Heart as well as central nervous system.⁹

So we should look for systemic as well as localized Demyelination.

Matrix Metalloproteinases dissolve Myelin

In 1993 researchers in Belgium¹⁰ demonstrated that toxins from Bordetella pertussis induce the enzyme Gelatinase B (also known as MMP-9) in an experimental model of Autoimmune Encephalomyelitis. Gelatinase B was found to digest Myelin basic protein in cerebrospinal fluid. In 2004 researchers in Italy found Endotoxin increases MMP-9 expression in Astrocytes and Microglia.¹¹

In 2019 upregulation of MMP-9 by Endotoxin was shown by Chen and coworkers to proceed via the TLR4 ERK1/2 (Extracellular signal-related kinases 1 and 2¹²) pathway.¹³

Note that in this paper the authors were interested in Heart Damage caused by Endotoxin (LPS):

These upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular mobility by LPS in cardiac fibroblasts may contribute to the development of cardiomyopathy, myocardial infarction, cardiac fibrosis and heart failure, particularly in patients with sepsis.

In 1996 it was known¹⁴ that Human Macrophage Metalloelastase (EC 3.4.24.65) degrades Elastin, type IV Collagen, type I Gelatin, Fibronectin, Laminin, Vitronectin and Proteoglycan.

Macrophage Metalloelastases are known to be upregulated by the Apex Cytokine Interleukin (IL)-1β resulting from the action of Endotoxin. In 2000 Pagenstecher and coworkers¹⁵ in Germany examined numerous organs after Endotoxin poisoning.

In 2003 Canadian and UK researchers found that Matrix Metalloproteinase 12 (MMP-12) expression after spinal cord trauma is deleterious and contributes to the development of secondary injury in Spinal cord injury.¹⁶ This paper includes an interesting discussion of potential MMP harm mechanisms known at the time.

Further details of Matrix Metalloproteinase 12 (MMP-12) expression controls were reported in 2022 by researchers in China.¹⁷

Phospholipase A2 in Demyelination

In 2006 it was found that Phospholipase A2 causes Spinal Cord Secondary Injury involving Demyelination.¹⁸

Endotoxin from Escherichia coli serotype 026:B6 is known to upregulate Phospholipase A2. ¹⁹

1. https://www.ninds.nih.gov/health-information/disorders/transverse-myelitis

2. https://www.cedars-sinai.org/health-library/diseases-and-conditions/t/transverse-myelitis.html

3. Demyelination, continued.

4. COVID-19 AND PASC: A DISEASE OF DEMYELINATION - AN UPDATE ON A UNIFYING THEORY OF SPIKE PROTEIN PATHOLOGY

5.

6. Shuper A, et al. 2000. Methotrexate Treatment Protocols and the Central Nervous System: Significant Cure With Significant Neurotoxicity. https://journals.sagepub.com/doi/10.1177/088307380001500902

7. Bingham J, et al. 2002. Methotrexate induces dose-dependent gut mucosal barrier dysfunction in an experimental animal model. Sylvester O'Halloran Surgical Scientific Meeting, Limerick.

8. Teh HS, et al. 2007. Transverse myelopathy following intrathecal administration of chemotherapy. https://pubmed.ncbi.nlm.nih.gov/17304378/

9. Hengstman GJD and Kusters B. 2011. Sudden cardiac death in multiple sclerosis caused by active demyelination of the medulla oblongata. https://journals.sagepub.com/doi/10.1177/1352458511408476

10. Gijbels K, et al. 1993. Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein. https://onlinelibrary.wiley.com/doi/10.1002/jnr.490360409

11. Liuzzi GM, et al. 2004. Anti-HIV drugs decrease the expression of matrix metalloproteinases in astrocytes and microglia. https://academic.oup.com/brain/article/127/2/398/347861

12. Lucas RM, et al. 2022. ERK1/2 in immune signalling. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704528/

13. Chen L-C, et al. 2019. ERK1/2 mediates the lipopolysaccharide-induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts. https://www.sciencedirect.com/science/article/abs/pii/S0009279718307531

14. Chandler S. et al. 1996. Macrophage Metalloelastase Degrades Matrix and Myelin Proteins and Processes a Tumour Necrosis Factor-α Fusion Protein. https://www.sciencedirect.com/science/article/abs/pii/S0006291X96916770

15. Pagenstecher A, et al. Regulation of Matrix Metalloproteinases and Their Inhibitor Genes in Lipopolysaccharide-Induced Endotoxemia in Mice. https://www.sciencedirect.com/science/article/pii/S0002944010645312

16. Wells JEA. 2003. An Adverse Role for Matrix Metalloproteinase 12 after Spinal Cord Injury in Mice. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740867/

17. Jiang Y, et al. 2022. ADAM-10 Regulates MMP-12 during Lipopolysaccharide-Induced Inflammatory Response in Macrophages. https://www.hindawi.com/journals/jir/2022/3012218/

18. Liu N-K, et al. A Novel Role of Phospholipase A2 in Mediating Spinal Cord Secondary Injury. https://onlinelibrary.wiley.com/doi/10.1002/ana.20798

19. Inger Lauritzen, Catherine Heurteaux and Michel Lazdunski. 1994. Expression of group II phospholipase A 2in rat brain after severe forebrain ischemia and in endotoxic shock. https://www.sciencedirect.com/science/article/abs/pii/0006899394907196