Thread by @LonnieRhea

Thread: A major barrier to progress in understanding the neurologic manifestations of #LymeDisease has been a lack of a tractable laboratory animal model to evaluate the mechanisms of central nervous system pathogenesis.

https://twitter.com/LonnieRhea/status/1356823740584054786

For decades we have seen study after study of Lyme arthritis. As it turns out the most frequently reported Lyme symptoms are neurological symptoms: memory loss and cognitive impairment, sleep impairment, psychiatric manifestations, headaches, neuropathy and more. 2/

This is the first study, to my knowledge, that shows how Borrelia burgdorferi gets into the central nervous system, how the immune system responds, and how the bacteria adapt to the immune system. #Lyme
Meet the researcher Catherine Brissette, Ph.D. globallymealliance.org/meet-researche…

So what the researchers show is that
1) B.b colonize the dura matter (a collagenous protective layer around the brain) within 7 days after infection, and
2) the location of the bite (eg the closer to the brain) effects the level of infection in the dura matter. #LymeDisease

3) The authors "did not find evidence of differences in CNS colonization between Borrelia species or intraspecies isolates in our model."

4) B.b. "burdens in the dura mater peaked at day 7 post-infection, and by days 14–28 were quickly reduced to low levels similar to that reported during late disseminated infection."

5) "Intriguingly, this early peak and clearance of spirochetes more closely resembles that reported in blood, rather than other peripheral tissues where burdens peak between 2–3 weeks post-infection and remain relatively higher throughout infection." #Lyme

6) "This rapid reduction of spirochete numbers in the dura mater suggests immune pressures similar to those seen in the blood, and was at least in part due to an adaptive immune response." #LymeDisease

7) "Nonetheless, the ability of B. burgdorferi to persist at low levels in this tissue for at least 75 days post-infection compared to undetectable levels in the blood during persistent infection may be due to bacterial interactions with these host proteins." #Lyme

While the researchers did not find cultivable B.b spirochetes w/in the brain they did map an increased inflammatory cytokine response, a transient IFN response was demonstrated that was not dependent on T cells or B cells.

The dura mater possesses: "blood vessels, lymphatic drainage, and a high density of resident immune cells including dendritic cells (DC), mast cells (MC), innate lymphocytes (ILCs), meningeal macrophages, T cells, and B cells capable of supporting a robust immune response"

Here I wrote about the connection between mast cells and neurological #LymeDisease lymedisease.org/mast-cells-neu…

Research from @JohnsHopkinsSPH demonstrating brain inflammation persists after Lyme disease treatment. lymedisease.org/brain-inflamma…

And research from Peter Novak and colleagues @harvardmed showing nerve damage (small fiber neuropathy) in patients with chronic symptoms of #LymeDisease lymedisease.org/nerve-damage-c… via @Lymenews

In conclusion "Although the potential pathologic consequences of the observed changes in the brain parenchyma are not clear in our model, our findings demonstrate that the brain is not simply a naïve bystander during B. burgdorferi infection of laboratory mice." 👏👏👏