Meningitis immunotherapy without antibiotics

Despite the widespread use of vaccines, bacterial meningitis is still associated with high mortality and neurological consequences, including hearing loss, focal neurological deficits, and cognitive impairment, which are estimated to occur in nearly half of surviving patients

Antibiotic treatment is necessary, but as the threat of antibiotic resistance increases, new treatment strategies are increasingly needed

Now, in a new study on mice, researchers at the University of Copenhagen and Lund University are able to use the body’s own immune cells to kill bacterial meningitis infections

"In a rat model, we observed that neutrophils, a type of immune cell, form a net-like structure in the membrane of the brain, that is, the meninges

Immune cells block the movement of brain fluid

Researchers say that immune cells that enter the brain membrane form a net that traps bacteria but also prevents the movement of cerebrospinal fluid

This fluid transport system was named the glymphatic system by Maiken Nedergaard, and its function has been shown to be essential to avoid the accumulation of protein plaques in Alzheimer's disease patients

Brain swelling, also called edema, is a life-threatening condition because the brain is contained in the skull

The Maiken Nedergaard group of the University of Copenhagen and Iben Lundgaard of Lund University collaborated for the first time and found that brain swelling in meningitis is caused by obstruction of the glial lymphatic system

Maiken Nedergaard, the lead author of the University of Copenhagen, said: "When immune cells enter the brain, they eat bacteria, but while doing so, immune cells also produce inflammatory components, including the web that causes swelling

"The most important aspect of our research is that it shows that meningitis can be treated by using an enzyme that degrades the neutrophil net

The hope of international clinical research

The researchers inferred that if the net is dissolved, leaving only immune cells without the net in the meninges, the cerebrospinal fluid can pass through the brain freely

The main component of the network structure is DNA, so the research team applied DNA cutting drugs (DNase)

"We injected DNase into mice infected with this bacteria, and we were able to prove that the net dissolves

Based on their findings, the research team now hopes to establish an international clinical study to investigate the role of DNase in the treatment of patients with bacterial meningitis

Maiken Nedergaard said: "We also want to study how metabolic waste removal is impaired in other brain diseases such as multiple sclerosis or viral meningitis

Chiara Pavan, Anna LR Xavier, Marta Ramos, Jane Fisher, Marios Kritsilis, Adam Linder, Peter Bentzer, Maiken Nedergaard, Iben Lundgaard.