Department of Internal Medicine, Turku University Central Hospital, Finland.
Despite a rapid increase in the number of patients with Lyme neuroborreliosis (LNB), its neuropathological aspects are poorly understood.
The objective of this study was evaluation of neuropathological, microbiological, and magnetic resonance imaging (MRI) findings in three patients with the Borrelia burgdorferi infection and neurological disease from whom brain tissue specimens were available.
Perivascular or vasculitic lymphocytic inflammation was detected in all specimens.
Large areas of demyelination in periventricular white matter were detected histologically and by MRI in one patient. The disease had a fatal outcome in this patient.
Brain MRI suggested malignancies in two patients before histopathological studies were carried out.
One of these two patients was a child with sudden hemiparesis. Another was a 40-year-old man presenting with epileptic seizures and MRI-detected multifocal lesions, which disappeared after repeated courses of antibiotics.
We conclude that cerebral lymphocytic vasculitis and multifocal encephalitis may be associated with B. burgdorferi infection.
The presence of B. burgdorferi DNA in tissue samples from areas with inflammatory changes indicates that direct invasion of B. burgdorferi may be the pathogenetic mechanism for focal encephalitis in LNB.
PMID: 9010017 [PubMed - indexed for MEDLINE]
***
Cannot believe that I have missed this abstract before. But then again I do not read Brain magazine every month Posts: 2557 | From home | Registered: Aug 2006
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Bea Seibert
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Keebler
Honored Contributor (25K+ posts)
Member # 12673
posted
- Wow! Sure has me respecting the state of my brain a lot more.
Thanks for this. While it was written 13 years ago, it's still an important article today. -
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Possible role of glial cells in the onset and progression of Lyme neuroborreliosis
Geeta Ramesh email, Juan T Borda email, Amy Gill email, Erin P Ribka email, Lisa A Morici email, Peter Mottram email, Dale S Martin email, Mary B Jacobs email, Peter J Didier email and Mario T Philipp email
Journal of Neuroinflammation 2009, 6:23doi:10.1186/1742-2094-6-23
Published: 25 August 2009 Abstract (provisional)
Background
Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.
Methods: We inoculated live B. burgdorferi into the cisterna magna of rhesus macaques and examined the inflammatory changes induced in the central nervous system (CNS), and dorsal root nerves and ganglia (DRG).
Results: ELISA of the cerebrospinal fluid (CSF) showed elevated IL-6, IL-8, CCL2, and CXCL13 as early as one week post-inoculation, accompanied by primarily lymphocytic and monocytic pleocytosis.
In contrast, onset of the acquired immune response, evidenced by anti-B. burgdorferi C6 serum antibodies, was first detectable after 3 weeks post-inoculation. CSF cell pellets and CNS tissues were culture-positive for B. burgdorferi. Histopathology revealed signs of acute LNB: severe multifocal leptomeningitis, radiculitis, and DRG inflammatory lesions.
Immunofluorescence staining and confocal microscopy detected B. burgdorferi antigen in the CNS and DRG. IL-6 was observed in astrocytes and neurons in the spinal cord, and in neurons in the DRG of infected animals. CCL2 and CXCL13 were found in microglia as well as in endothelial cells, macrophages and T cells.
Importantly, the DRG of infected animals showed significant satellite cell and neuronal apoptosis.
Conclusions: Our results support the notion that innate responses of glia to B. burgdorferi initiate/mediate the inflammation seen in acute LNB, and show that neuronal apoptosis occurs in this context.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
[ 11-12-2009, 10:23 AM: Message edited by: lou ]
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posted
Neuroscience. 2008 Jul 25. [Epub ahead of print]
Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: Underlying mechanisms.
Teeling JL, Perry VH.
CNS Inflammation Group, School of Biological Sciences, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
We have all at some time experienced the non-specific symptoms that arise from being ill following a systemic infection. These symptoms, such as fever, malaise, lethargy and loss of appetite are often referred to as "sickness behavior" and are a consequence of systemically produced pro-inflammatory mediators.
These inflammatory mediators signal to the brain, leading to activation of microglial cells, which in turn, signal to neurons to induce adaptive metabolic and behavioral changes. In normal healthy persons this response is a normal part of our defense, to protect us from infection, to maintain homeostasis and causes no damage to neurons.
However, in animals and patients with chronic neurodegenerative disease, multiple sclerosis, stroke and even during normal aging, systemic inflammation leads to inflammatory responses in the brain, an exaggeration of clinical symptoms and increased neuronal death.
These observations imply that, as the population ages and the number of individuals with CNS disorders increases, relatively common systemic infections and inflammation will become significant risk factors for disease onset or progression. In this review we discuss the underlying mechanisms responsible for sickness behavior induced by systemic inflammation in the healthy brain and how they might be different in individuals with CNS pathology.
PMID: 18706982 [PubMed - as supplied by publisher
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Microglial activation and its implications in the brain diseases.
Dheen ST, Kaur C, Ling EA.
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore 117597.
An inflammatory process in the central nervous system (CNS) is believed to play an important role in the pathway leading to neuronal cell death in a number of neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, prion diseases, multiple sclerosis and HIV-dementia.
The inflammatory response is mediated by the activated microglia, the resident immune cells of the CNS, which normally respond to neuronal damage and remove the damaged cells by phagocytosis.
Activation of microglia is a hallmark of brain pathology. However, it remains controversial whether microglial cells have beneficial or detrimental functions in various neuropathological conditions.
The chronic activation of microglia may in turn cause neuronal damage through the release of potentially cytotoxic molecules such as proinflammatory cytokines, reactive oxygen intermediates, proteinases and complement proteins.
Therefore, suppression of microglia-mediated inflammation has been considered as an important strategy in neurodegenerative disease therapy. Several anti-inflammatory drugs of various chemical ingredients have been shown to repress the microglial activation and to exert neuroprotective effects in the CNS following different types of injuries.
However, the molecular mechanisms by which these effects occur remain unclear. In recent years, several research groups including ours have attempted to explain the potential mechanisms and signaling pathways for the repressive effect of various drugs, on activation of microglial cells in CNS injury.
We provide here a comprehensive review of recent findings of mechanisms and signaling pathways by which microglial cells are activated in CNS inflammatory diseases. This review article further summarizes the role of microglial cells in neurodegenerative diseases and various forms of potential therapeutic options to inhibit the microglial activation which amplifies the inflammation-related neuronal injury in neurodegenerative diseases.
PMID: 17504139 [PubMed - indexed for MEDLINE
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Department of BiochemistryTrinity College Institute of Neuroscience, Trinity College Dublin, Republic of Ireland.
BACKGROUND: Chronic neurodegeneration results in microglial activation, but the contribution of inflammation to the progress of neurodegeneration remains unclear. We have shown that microglia express low levels of proinflammatory cytokines during chronic neurodegeneration but are "primed" to produce a more proinflammatory profile after systemic challenge with bacterial endotoxin (lipopolysaccharide [LPS]).
METHODS: Here, we investigated whether intraperitoneal (IP) challenge with LPS, to mimic systemic infection, in the early stages of prion disease can 1) produce exaggerated acute behavioral (n = 9) and central nervous system (CNS) inflammatory (n = 4) responses in diseased animals compared with control animals, and 2) whether a single LPS challenge can accelerate disease progression (n = 34-35).
RESULTS: Injection of LPS (100 mug/kg), at 12 weeks postinoculation (PI), resulted in heightened CNS interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-beta (IFN-beta) transcription and microglial IL-1beta translation in prion-diseased animals relative to control animals. This inflammation caused exaggerated impairments in burrowing and locomotor activity, and induced hypothermia and cognitive changes in prion-diseased animals that were absent in LPS-treated control animals. At 15 weeks PI, LPS (500 mug/kg) acutely impaired motor coordination and muscle strength in prion-diseased but not in control animals. After recovery, these animals also showed earlier onset of disease-associated impairments on these parameters.
CONCLUSIONS: These data demonstrate that transient systemic inflammation superimposed on neurodegenerative disease acutely exacerbates cognitive and motor symptoms of disease and accelerates disease progression. These deleterious effects of systemic inflammation have implications for the treatment of chronic neurodegeneration and associated delirium.
PMID: 18801476 [PubMed - as supplied by publisher
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Vermont_Lymie
Frequent Contributor (1K+ posts)
Member # 9780
posted
Wow, thanks lou for posting all of these abstracts. Got my reading cut out for me today.
You are very welcome Bea and Keebler. I am amazed this information was in a major neuro journal back in 1996, but still the astounding and inexcusable ignorance by the IDSA and many if not most neurologists.
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posted
And somewhere I have one that shows peripheral inflammation can be transferred to the CNS.
Posts: 8430 | From Not available | Registered: Oct 2000
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
"Perivascular or vasculitic lymphocytic inflammation was detected in all specimens."
"H16" is a category, a group, that designates
vascular problems.
It appears Bb camps out in the basement membranes which are here (picture):
Very logical...close to a nutrient supply.
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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Hoosiers51
Frequent Contributor (1K+ posts)
Member # 15759
posted
Hey V_L!
I just tried sending you a PM when I saw your post, but your box is full. I'll just ask you right here because it would probably be easier if you don't want to hassle with emptying your box....
Could you let me know what dose of Quinine you were on for 7 days? I have heard 650mg X 3 daily is sometimes used short term.
My dose right now is 324 mg X 3 daily, and it is actually feeling kind of weak.
Sorry to derail the thread! You can PM me! Thanks...
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Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Lou..inflammation AND infection.
We have to address BOTH...BIGTIME.
Which is why/how docs in Romania were able to halt early onset lyme by restoring Mg levels (Mg is an anti-inflammatory and anti-histamine) AND give abx. Both via IV.
They greatly tamed down inflammation AND hit Bb with abx.
Posts: 9424 | From Sunshine State | Registered: Mar 2001
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posted
Thanks marnie. I sure need to find a way to tame the inflammation caused by the herx. This exacerbates the muscle wasting/neuron death and is the reason I can't do killing doses of abx.
However, I am already on high doses of Mg orally. Will IV do anything better than that? And what was the dosage used by the Rumanians? Is there a published article on their treatment?
[ 11-13-2009, 10:51 AM: Message edited by: lou ]
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