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Philadelphia, PA, April 16, 2015

About 15% of patients with Lyme disease develop peripheral and central nervous system involvement, often accompanied by debilitating and painful symptoms. New research indicates that inflammation plays a causal role in the array of neurologic changes associated with Lyme disease, according to a study published in The American Journal of Pathology. The investigators at the Tulane National Primate Research Center and Louisiana State University Health Sciences Center also showed that the anti-inflammatory drug dexamethasone prevents many of these reactions.

“These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis,” explained Mario T. Philipp, PhD, Professor of Microbiology and Immunology and chair of the Division of Bacteriology and Parasitology at Tulane National Primate Research Center (Covington, LA).

In the latest example of bacteria being "literally everywhere," scientists appear to have found evidence of microbes living harmlessly in our brains.

For the study, presented last week at the scientific meeting Neuroscience 2018, the researchers looked at high-resolution images of slices of postmortem human brain tissue, where they found signs of bacteria, according to Science Magazine.

The findings are preliminary, and more work is needed to completely rule out the possibility that the brain samples were somehow contaminated after death, said the researchers, from the University of Alabama at Birmingham (UAB). [5 Ways Gut Bacteria Affect Your Health]

In the new study, the researchers analyzed samples from 34 postmortem analyses of human brains and found bacteria in every brain. Importantly, the researchers found no signs of inflammation or bacterial disease in the brains they examined.

The brain is a protected environment, partially walled off from the contents of the bloodstream by a network of cells that surround its blood vessels. Bacteria and viruses that manage to penetrate this blood-brain barrier can cause life-threatening inflammation. Some research has suggested distant microbes—those living in our gut—might affect mood and behavior and even the risk of neurological disease, but by indirect means. For example, a disruption in the balance of gut microbiomes could increase the production of a rogue protein that may cause
Parkinson’s disease if it travels up the nerve connecting the gut to the brain.

Infections of the brain can be caused by viruses, bacteria, fungi, or, occasionally, protozoa or parasites.

bacterial meningitis spreads to the brain itself, causing encephalitis. Similarly, viral infections that cause encephalitis often also cause meningitis. Technically, when both the brain and the meninges are infected, the disorder is called meningoencephalitis. However, infection that affects mainly the meninges is usually called meningitis, and infection that affects mainly the brain is usually called encephalitis.

Usually in encephalitis and meningitis, infection is not confined to one area. It may occur throughout the brain or within meninges along the entire length of the spinal cord and over the entire brain.

Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease

Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls.

Keywords: Alzheimer's disease, bacteria, Borrelia burgdorferi, dementia, infection, Lyme disease, periodontal pathogen, spirochetes, Treponema, syphilis

DISCUSSION

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Blood-Brain Barrier Disruption in Response to Borrelia Infection in Brain Tissue
Only three consensus pathways were perturbed in the brain tissue by our dual-method pipeline. Moreover, these pathways had fewer differentially expressed genes compared to the heart tissue results (Table 1). This is expected: because B. burgdorferi does not actively infect murine brain tissue (Radolf et al., 2012), a less cohesive response occurs upon host infection as a variety of cell types are responding to inflammation, not generating an inflammatory response. We observed perturbations in calcium signaling, gap junction, and melanogenesis. Calcium signaling has been shown to influence bacterial infection (Soderblom et al., 2005; TranVan Nhieu et al., 2004). We propose that this phenomenon is exploited by B. burgdorferi to cross the blood-brain barrier (Coureuil et al., 2013; Grab et al. 2005; Halperin, 2015), even if these bacteria fail to establish infection (Radolf et al., 2012) once across the barrier. This perturbation of the blood-brain barrier could be used to study human neuroborreliosis. Previous studies indicate that neurological symptoms exhibited by Borrelia infection in humans may be attributed to the success of Borrelia in crossing the blood-brain barrier and attacking the CNS (Grab et al., 2009). Our results are consistent with these findings, suggesting that the bacterium may also disrupt the blood-brain barrier in mice by dysregulated calcium signaling and gap junctions. This suggests the potential of targeting bacterial crossing of blood-brain barrier for therapeutic use.
[…..].
They found over 30 genes to be significantly upregulated, including Cxcl9, H2-Eb1, Ccl8, H2-Aa, Zbp1 and Igtp. We observed these genes to be also upregulated in Lyme heart infection. However, no genes were found in both the T. gondii study and on our list of DEGs in the brain. [color=#0000FF]This suggests more work needs to be done to understand the molecular basis of neuroborreliosis.[/color]
In conclusion, we present a dual-method pipeline to analyze the host transcriptome Borrelia infection using RNA-seq. Many immune response-related genes were differentially expressed in heart tissue and far fewer were identified in the brain. We propose that Borrelia may disrupt the blood-brain barrier in mice and induces a peripheral inflammatory cascade.
First, although infection was not established in the brain, the tissue is affected as many genes are differentially expressed and we found that neuronal gap junctions and calcium signaling are disrupted. This is a hallmark of loss of integrity of the blood-brain barrier. Thus, the damage is occurring irrespective of direct brain infection. Moreover, this suggests that in human infection, the crossing of the blood-brain barrier and infection of the central nervous system are two events. It may be possible to study Borrelia’s effect on the blood-brain barrier in mice, even though the central nervous system is not infected in a mouse
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Challenges facing diagnosis and treatment of Lyme are significant.
Prolonged symptoms after antibiotic treatment are still afflicting a small percentage of patients, making the topic of “chronic Lyme disease” interesting but understudied. Although the mouse is not a perfect model of human Lyme disease, we show that the mouse can be used to examine unique features of Borrelia infection and the crossing of the blood-brain barrier. A thorough molecular study to explore these pathways over time is needed to elucidate the etiology of lingering Lyme symptoms in the host in order to improve patient outcome.

More than 1 in 10 people successfully treated with antibiotics for Lyme disease go on to develop chronic, sometimes debilitating, and poorly understood symptoms of fatigue and brain fog that may last for years after their initial infection has cleared up. Now, in a small study, Johns Hopkins Medicine researchers report they have used an advanced form of brain scan to show that 12 people with documented post-treatment Lyme disease syndrome (PTLDS) all show elevation of a chemical marker of widespread brain inflammation, compared with 19 healthy controls.

Two kinds of pain

Basically, there are two types of pain: acute and chronic. Acute pain is caused by the stimulus of pain sensory nerves in the body that send a signal up your spinal cord to your brain, which registers as pain (like stepping on a tack or smacking your elbow).

Chronic pain (or pain that persists after or in the absence of injury) is caused by the misfiring of nerves. In the brain, over-active glia are known to contribute to persistent pain. The JH study shows glial inflammation is also related to persistent cognitive symptoms. So, it makes sense that Lyme patients report a lot of pain and neurological symptoms.

Findings correspond with MyLymeData

The symptoms and poor quality of life scores of the PTLDS patients in the JH study correspond with the published results of Phase 1 of the MyLymeData study. It collected data from 3,900 physician-diagnosed Lyme disease patients who were still ill.

When asked to name their worst symptoms, these MyLymeData participants most frequently reported neurological (84%), fatigue (62%), and musculoskeletal-associated symptoms (57%).

A prior LymeDisease.org study confirmed what this JH study shows: chronic Lyme disease is associated with a worse quality of life than most other chronic illnesses, including congestive heart failure, diabetes, multiple sclerosis and arthritis.

Results

Of the 66 patients with neuro-Lyme disease, 11 showed findings on MR imaging. Sixty-three of the 66 patients were examined before and after the administration of intravenous contrast material. Three patients showed nerve-root or meningeal enhancement (Figs 1 and 2), seven patients demonstrated foci of T2 prolongation in the cerebral white matter without enhancement (Figs 3 and 4), and one patient had an enhancing lesion with edema