Meningitis: Researchers find possible treatment strategy without
antibiotics

Date:
October 18, 2021
Source:
University of Copenhagen - The Faculty of Health and Medical
Sciences
Summary:
Meningitis is a very serious brain infection with limited treatment
options. In a new study performed in rats, researchers present an
alternative treatment based on immune cells that helps rinse away
toxins that accumulate during the infection.



FULL STORY ========================================================================== Fever, headache, confusion, seizures, amputations or death. Meningitis
is a very serious brain infection that can affect the body in many ways
and needs to be treated within 24 hours of contracting the disease. The
World Health Organization estimates that there are close to three million
cases per year.

Between the four main causes of meningitis, the WHO is particularly
concerned about bacterial meningitis, which is caused by the infectious bacteria Streptococcus pneumoniae.


========================================================================== Despite widespread implementation of vaccines, bacterial meningitis is
still associated with a high mortality rate and neurological consequences including hearing loss, focal neurological deficits and cognitive
impairment, estimated to occur in close to half of surviving patients.

Antibiotic treatment is necessary, but with the increasing threat
of antibiotic resistance, there is a growing need for new treatment
strategies.

Now, in a new study performed in rats, researchers from the University
of Copenhagen and Lund University were able to utilize the body's own
immune cells to kill the bacterial meningitis infection.

"In a rat model we observed that the neutrophils, a type of immune cells,
form a net-like structure in the brain's membrane, the meninges. But this particular net-structure also causes brain swelling and prevents removal
of waste products. We discovered, that if we dissolved the structure
-- not the immune cells -- the immune cells still kill the meningitis
bacteria but without causing brain swelling," says Ph.D. Chiara Pavan,
first author on the study.

Immune cells block movement of brain fluid The researchers show that
immune cells entering the brain's membrane, create a net that traps
bacteria but also blocks the movement of cerebrospinal fluid.

The brain is constantly cleaned by the cerebrospinal fluid that enters
the tissue along blood vessels and is responsible for clearing out waste products made by the active brain cells.



==========================================================================
This fluid transport system was named the glymphatic system by Maiken Nedergaard, and its function has been shown to be critical for avoiding accumulation of protein plaques that accumulates in patients with
Alzheimer disease. Glymphatic transport of cerebrospinal fluid is also important for avoiding brain swelling in acute diseases such as stroke.

Brain swelling, also called edema, is a life threatening condition
because the brain is contained within the skull. The swelling compress
blood vessels resulting in loss of the brain tissue, which is fatal when
the brain regions that controls breathing stops working.

That brain swelling in meningitis is caused by blockage of the glymphatic system is now shown for the first time in collaboration between Maiken Nedergaards group at the University of Copenhagen and Iben Lundgaard at
Lund University.

"When the immune cells enter the brain, they eat the bacteria, but
while doing so the immune cells also produce inflammatory components,
including nets that cause swelling," says Maiken Nedergaard, the lead
author from the University of Copenhagen.

"The most important aspects of our study is that it suggests that
meningitis can be treated by administration of an enzyme that degrades
the neutrophil nets. Enzymatic removal of nets eliminated the often fatal accumulation of fluid in the brain in rats with bacterial meningitis. This novel treatment can be combined with antibiotics if needed," she says.



==========================================================================
Hope for an international clinical study The researchers theorized that
if the nets were dissolved, leaving just the immune cells without their
nets in the meninges, it would allow the cerebrospinal fluid to pass
the brain freely.

The net-like structures consist mainly of DNA, so the research team
applied drugs for cutting up DNA, so-called DNase. They gave DNase to
the rats infected with pneumococcus bacteria, which causes bacterial meningitis.

"We administered DNase to rats infected with the bacteria, and we were
able to show that the nets dissolved. The treatment reduced brain
swelling and helped in removing metabolic waste production from the
infected brain. In contrast, antibiotic treatment did not have an effect
on brain swelling or waste clearance," says Maiken Nedergaard.

Based on their results, the research team now hopes to set up an
international clinical study to investigate DNase in the treatment of
patients with bacterial meningitis. Antibiotic resistant is increasing at
an alarming rate and the drug the researchers use here is a promising alternative, and has already been approved for human use in other
neurological diseases.

"We would also like to investigate how metabolic waste products removal
is impaired in other disease of the brain such as multiple sclerosis or
viral meningitis," says Maiken Nedergaard.

========================================================================== Story Source: Materials provided by University_of_Copenhagen_-_The_Faculty_of_Health_and
Medical_Sciences. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Chiara Pavan, Anna L. R. Xavier, Marta Ramos, Jane Fisher, Marios
Kritsilis, Adam Linder, Peter Bentzer, Maiken Nedergaard, Iben
Lundgaard.

DNase Treatment Prevents Cerebrospinal Fluid Block in Early
Experimental Pneumococcal Meningitis. Annals of Neurology, 2021;
90 (4): 653 DOI: 10.1002/ana.26186 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211018172238.htm

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