December 9, 2022

Researchers find possible treatment strategy without antibiotics – ScienceDaily


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Fever, headache, confusion, convulsions, amputations or death. Meningitis is a very serious brain infection that can affect the body in several ways and should be treated within 24 hours of contracting the disease. The World Health Organization estimates that there are nearly three million cases per year. Among the four main causes of meningitis, WHO is particularly concerned about bacterial meningitis, which is caused by the infectious bacteria Streptococcus pneumoniae.

Despite the widespread implementation of vaccines, bacterial meningitis is still associated with a high death rate and neurological consequences, including hearing loss, focal neurological deficits, and cognitive impairment, which occur in almost half of patients. survivors.

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

Now, in a new study in rats, researchers at the University of Copenhagen and Lund University were able to use the body’s own immune cells to kill bacterial meningitis infection.

“In a rat model, we observed that neutrophils, a type of immune cell, form a net-like structure in the brain’s membrane, the meninges. But this particular net structure also causes swelling of the brain and prevents waste disposal. We have discovered, that if we dissolve the structure – and not the immune cells – the immune cells still kill the meningitis bacteria but without causing swelling in the brain, ”explains Ph.D. Chiara Pavan, first author of the study.

Immune cells block the movement of brain fluid

Researchers show that immune cells that enter the brain membrane create a net that traps bacteria but also blocks the movement of cerebrospinal fluid. The brain is constantly cleansed by cerebrospinal fluid, which enters the tissues along the blood vessels and is responsible for removing wastes produced by active brain cells.

This fluid transport system was named the glymphatic system by Maiken Nedergaard, and its function has been shown to be essential in preventing the build-up of protein plaques that build up in patients with Alzheimer’s disease. Lymphatic transport of cerebrospinal fluid is also important to prevent swelling of the brain in acute illnesses such as stroke.

Swelling of the brain, also called edema, is a life-threatening condition because the brain is contained within the skull. The swelling compresses the blood vessels, causing loss of brain tissue, which is fatal when the areas of the brain that control breathing stop working.

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

“When immune cells enter the brain, they eat bacteria, but in doing so, immune cells also produce inflammatory components, including threads that cause swelling,” says Maiken Nedergaard, senior author at the University. of Copenhagen.

“The most important aspect of our study is that it suggests that meningitis can be treated by administration of an enzyme that breaks down the neutrophil threads. Enzymatic removal of the threads eliminated the often fatal build-up of fluid. in the brain in rats with bacterial meningitis. This novel treatment can be combined with antibiotics if necessary, “she said.

Hope for an international clinical study

The researchers hypothesized that if the threads were dissolved, leaving only immune cells without their threads in the meninges, it would allow cerebrospinal fluid to flow freely through the brain.

The net-like structures are mostly made up of DNA. The research team therefore applied drugs to cut DNA, called DNase. They gave DNase to rats infected with the pneumococcal bacteria, which causes bacterial meningitis.

“We administered DNase to rats infected with the bacteria and we were able to show that the fillets dissolved. The treatment reduced swelling in the brain and helped clear metabolic waste production from the infected brain. On the other hand, the antibiotic treatment had no effect on swelling of the brain or elimination of waste, ”explains Maiken Nedergaard.

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

“We would also like to study how the elimination of metabolic waste is impaired in other brain diseases such as multiple sclerosis or viral meningitis”, explains Maiken Nedergaard.

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