Researchers find link to treat Gulf War illness

A team of researchers, hailing from undivided Dakshina Kannada district, at the Department of Molecular and Cellular Medicine at the Texas A & M College of Medicine, Texas, USA, have found some link to the possible treatment of chronic neuroinflammation that results in brain dysfunction associated with Gulf War Illness.

The team is led by Ashok Shetty and Dr Madhu L N. Shetty, professor with the Department of Molecular Medicine at the Texas A&M College of Medicine and associate director of the Institute for Regenerative Medicine, is a native of Kundapur in Udupi district.

Dr Madhu L N, first author of the research article, is a Post Doctoral Fellow at Texas A & M College of Medicine and a former assistant professor at St Aloysius College in Mangaluru.

In an email interaction with DH, Dr Madhu said the research links neuroinflammation from Gulf War illness to HMGB1 (High mobility group box 1 is an intracellular protein) and complement activation.

The scientific study was recently published in peer-reviewed Brain Behavior Immunity (Brain, Behavior and Immunity https://www.sciencedirect.com /science/ article/ pii/ S0889159119304763?via%3Dihub).

Over the years, veterans from the first Gulf War suffered from different psychological and physical symptoms and treatment to the illness was difficult due to its range of ailments.

“We knew several of the wartime chemicals in question could enter the brain through a leaky blood-brain barrier, which caused a build-up of a neurotransmitter called acetylcholine,” said Dr Shetty.

He added, “The acetylcholine typically excites neurons but can also make neurons sick or even die due to too much excitation, which creates the inflammation.” However, the mechanisms underlying chronic brain inflammation in Gulf War Illness was mostly unknown.

The study, funded by the Department of Defence of US, had used animal models of Gulf War illness to recreate how the illness occurred and inform experts on the mechanisms of inflammation, Dr Shetty said.

Researchers exposed the models to similar chemicals and waited for 10 months, which is equivalent to 25 to 30 years in a human life or roughly the time since the First Gulf War.

“The researchers showed that HMBG1 can transport into the cytoplasm and leak into the extracellular space of a living cell. From there, the HMBG1 creates a chain reaction that ultimately releases toxic substances that can make neurons sick and die. Firstly, the HMBG1 activates certain receptors on microglial cells found in the central nervous system. Those cells then release proinflammatory cytokines, which, when in too great of a quantity, can eventually deteriorate brain tissue and cause cognitive and mood problems,” explained Dr Madhu.

As a part of the immune system, the complement system increases the opportunity for antibodies to target invading cells by increasing inflammation.

However, when the complement system is triggered by an injury or exposure to chemicals, it will develop an autoimmune-type reaction that maintains a persistent inflammation within the body, he said.

The research findings and methods used in the study can be applied to Gulf war veterans.

A “liquid biopsy” approach using the the characterization of brain-derived vesicles in the blood can be useful in clinical trials as it provides a minimally invasive way to monitor persistence or progression of brain inflammation in patients/veterans of Gulf War Illness, felt Dr Shetty and Dr Madhu.

To continue, Dr Shetty is hoping to collaborate with investigators who have a blood bank of samples taken from patients and extend the current funding of this study through another grant from the Department of Defence.