passing REAL MS to mice. New report 2020. An IgG-driven kind of MS found.

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frodo
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passing REAL MS to mice. New report 2020. An IgG-driven kind of MS found.

Post by frodo » Wed Apr 22, 2020 12:41 am

There have been several reports previously about passing real PPMS (not RRMS nor SPMS) to mice by injections of CSF from patients. See for instance this, this, this or this

Here we have new one. In this case, before passing the CSF to the mice, they have depleted it from IgG, and they have observed that the effect dissapears.

1-018 – IgG Depletion Ameliorates Pathogenic Effects of Primary Progressive MS CSF. Joseph Michael Beaty

https://multiple-sclerosis-research.org ... -bad-news/

Background

MS is characterized by inflammatory demyelination, astrogliosis and axonal loss in the CNS. Approximately 15% of MS patients are diagnosed with PPMS, which is characterized by unremitting disease progression from disease onset. We have previously reported that intrathecal delivery of PPMS CSF induces motor deficits and spinal cord pathology in mice. Here, we investigated whether depletion of IgGs from PPMS CSF prior to intrathecal administration would improve functional outcome and spinal cord pathology in mice.

Objective
To assess whether the pathogenic effects of primary progressive multiple sclerosis (PPMS) cerebrospinal fluid (CSF) are antibody-mediated.

Design Methods

CSF samples obtained from PPMS patients were incubated with DynabeadsTM Protein A for 1 hour at 4oC and Coomassie staining was performed to verify IgG reduction. PPMS CSF and IgG-depleted PPMS CSF was administered to mice intrathecally. Mice underwent laminectomies at cervical levels 4 and 5, then 3µl CSF was injected under the dura mater into the subarachnoid space. Control mice were injected with saline or CSF from healthy individuals. At 1 day post injection (DPI), functional deficits were assessed by evaluating forelimb grip strength, reaching accuracy and tail rigidity. Mice were then immediately perfused and spinal cords were processed for histological analyses.

Results
At 1DPI, PPMS CSF-injected mice exhibited significantly higher motor deficit scores and weaker grip strength compared to IgG-depleted PPMS CSF-injected mice and control mice. Demyelination, reactive astrogliosis and axonal damage were observed in the cervical spinal cords of PPMS CSF-injected mice, as demonstrated by luxol fast blue, GFAP and SMI-32 staining, respectively. However, these pathological changes were not observed in spinal cords of IgG-depleted PPMS CSF-injected mice or controls.

Conclusions
Intrathecal administration of IgG-depleted PPMS CSF does not result in motor deficits or pathology, suggesting that the pathogenic effects induced by PPMS CSF are antibody-mediated.

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