Fever, headache, confusion, seizures, amputation or death. Meningitis is a very serious brain infection that can affect the body in a variety of ways and should be treated within 24 hours of getting sick. The World Health Organization estimates that there are nearly 3 million cases annually. Of the four main causes of meningitis, WHO is particularly concerned about bacterial meningitis caused by infectious bacteria. Streptococcus pneumoniae..
Bacterial meningitis remains with high mortality and neurological effects such as deafness, localized neuropathy, and cognitive impairment, despite the widespread use of vaccines, and occurs in nearly half of surviving patients. It is estimated.
Treatment with antibiotics is required, but as the threat of antibiotic resistance increases, so does the need for new treatment strategies.
Currently, in a new study conducted in rats, researchers at the University of Copenhagen and Lund University have been able to utilize their own immune cells to kill bacterial meningitis infections.
“In a rat model, we observed that neutrophils, a type of immune cell, form a reticulated structure in the meninges of the brain, but this particular reticulated structure causes swelling of the brain. It causes and prevents the removal of waste products. Even if the structure is lysed instead of the immune cells, the immune cells kill the meningitis bacteria but do not cause swelling of the brain, “Ph.D. said. I am. Chiara Pavan, the first author of the study.
Immune cells block the movement of cerebrospinal fluid
Researchers have shown that when immune cells enter the membrane of the brain, they not only trap bacteria, but also create a net that blocks the movement of cerebrospinal fluid. The brain is constantly purified by cerebrospinal fluid, which enters tissues along blood vessels, and is responsible for clearing waste products produced by active brain cells.
This fluid transport system was named the Glymptic System by Maiken Nedergaard, and its function has been shown to be important in avoiding the accumulation of protein plaques that accumulate in patients with Alzheimer’s disease. Lymphatic transport of cerebrospinal fluid is also important to avoid swelling in acute illnesses such as stroke.
Swelling of the brain, also known as edema, is a life-threatening condition because the brain is contained within the skull. Swelling compresses blood vessels, resulting in loss of brain tissue. This is fatal when the areas of the brain that control breathing fail.
The cause of meningitis cerebral edema by obstruction of the lymphatic system was first shown in a collaboration between the Maiken Nedergaards group at the University of Copenhagen and Iben Lundgaard at Lund University.
“When immune cells enter the brain, they eat bacteria, while they also produce inflammatory components such as swelling-causing nets,” said Maiken Nedergaard, lead author at the University of Copenhagen. I have.
“The most important aspect of our study is that it suggests that the administration of enzymes that break down the neutrophil network can treat meningitis. Enzymatic removal of the network is of bacterial meningitis. Eliminating the often deadly buildup of fluid in the rat’s brain. This novel can be combined with enzymes if needed, “she says.
Expectations for international clinical research
Researchers have theorized that cerebrospinal fluid is free to pass through the brain when the reticulum is lysed, leaving only non-reticulated immune cells in the meninges.
Because the network structure is predominantly composed of DNA, the research team applied a drug to cleave DNA, the so-called DNase. They gave DNase to rats infected with Streptococcus pneumoniae, which causes bacterial meningitis.
“When we administered DNase to bacteria-infected rats, we were able to show that the net had dissolved. This treatment helped reduce swelling in the brain and remove the production of metabolic waste products from the infected brain. In contrast, antibiotic treatment was ineffective. Removal of cerebral edema and waste products, “said Maiken Nedergaard.
Based on their results, the research team now wants to launch an international clinical study to investigate DNases in the treatment of patients with bacterial meningococcus. Antibiotic resistance is increasing at an alarming rate, and the drugs used here by researchers are promising alternatives and have already been approved for use in humans in other neurological disorders.
“We also want to investigate how other diseases of the brain, such as multiple sclerosis and viral meningitis, impair the removal of metabolic waste products,” said Maiken Nedergaard.