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COVID cognitive symptoms linked to cerebrospinal fluid

The study could help increase understanding of ‘brain fog’ among people recovering from COVID and those with Long COVID

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Cognitive symptoms experienced by people recovering from COVID-19 may be linked to abnormalities found in cerebrospinal fluid, new research has revealed. 

The new findings around the role of cerebrospinal fluid, which saw similar changes in those recovering from a mild bout of COVID as people with other infectious diseases, may provide new insight into how the SARS-CoV-2 virus impacts the brain.

‘Brain fog’ has become recognised as a common after effect of COVID and symptom of Long COVID, which can cause varying degrees of cognitive issues.

In a small study with 32 adults, comprising 22 with cognitive symptoms and ten control participants without, researchers from UC San Francisco and Weill Cornell Medicine, New York, analysed the cerebrospinal fluid of 17 of the participants who consented to lumbar puncture. 

All participants had had COVID but had not required hospitalisation.

They found that ten of 13 participants with cognitive symptoms had anomalies in their cerebrospinal fluid – but all four of the cerebrospinal samples from participants with no post-COVID cognitive symptoms were normal. 

Participants with these symptoms presented with executive functioning issues, said senior author Dr Joanna Hellmuth, of the UCSF Memory and Aging Center. 

“They manifest as problems remembering recent events, coming up with names or words, staying focused, and issues with holding onto and manipulating information, as well as slowed processing speed,” she said.

Examinations of the cerebrospinal fluid revealed elevated levels of protein, suggesting inflammation, and the presence of unexpected antibodies found in an activated immune system. 

Some were found in the blood and cerebrospinal fluid, implying a systemic inflammatory response, or were unique to the cerebrospinal fluid, suggesting brain inflammation. 

While the targets of these antibodies are unknown, it is possible that these could be “turncoat” antibodies that attack the body itself.

“It’s possible that the immune system, stimulated by the virus, may be functioning in an unintended pathological way,” said Dr Hellmuth, who is principal investigator of the UCSF Coronavirus Neurocognitive Study and is also affiliated with the UCSF Weill Institute for Neurosciences. 

“This would be the case even though the individuals did not have the virus in their bodies,” she said, noting that the lumbar punctures took place on average ten months after the participants’ first COVID symptom.

The researchers also found that the participants with cognitive symptoms had an average of 2.5 cognitive risk-factors, compared with an average of less than one risk factor for participants without the symptoms. 

These risk-factors included diabetes and hypertension, which can increase the risk of stroke, mild cognitive impairment and vascular dementia; and a history of ADHD, which may make the brain more vulnerable to executive functioning issues. Other risk factors included anxiety, depression, a history of  heavy alcohol or repeated stimulant use, and learning disabilities.

Research

New hope in treatment of brain cancer GBM

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Findings from pioneering new research suggest there could be a new approach to treating one of the most common and devastating forms of brain cancer in adults – Glioblastoma Multiforme (GBM). 

In a seven-year study, scientists from the University of Surrey show that a short chain of amino acids (the HTL-001 peptide) is effective at targeting and inhibiting the function of a family of genes responsible for the growth of GBM – Hox genes. The study was conducted in cell and animal models.

The HTL-001 peptide used in the study has undergone safety testing and is suitable for patient trials. These trials are now being considered in GBM and other cancers.

The study adds further progress and gives new hope in an area where advances have not been as rapid as in other cancer types. 

Professor Hardev Pandha, project lead and Professor of Medical Oncology at the University of Surrey, said: “People who suffer from GBM have a five per cent survival rate over a five-year period – a figure that has not improved in decades. 

“While we are still early in the process, our seven-year project offers a glimmer of hope for finding a solution to Hox gene dysregulation, which is associated with the growth of GBM and other cancers, and which has proven to be elusive as a target for so many years.”

Ironically, Hox genes are responsible for the healthy growth of brain tissue but are ordinarily silenced at birth after vigorous activity in the growing embryo. 

However, if they are inappropriately ‘switched on’ again, their activity can lead to the progression of cancer. Hox gene dysregulation has long been recognised in GBM.

The project was carried out in collaboration with the universities of Surrey, Leeds and Texas, and HOX Therapeutics, a University of Surrey start-up company based on the University’s Surrey Research Park.

Professor Susan Short, co-author of the study from the University of Leeds, said: “We desperately need new treatment avenues for these aggressive brain tumours. 

“Targeting developmental genes like the HOX genes that are abnormally switched on in the tumour cells could be a novel and effective way to stop glioblastomas growing and becoming life-threatening.”

James Culverwell, CEO of HOX Therapeutics, said: “HOX Therapeutics is excited to be associated with this project and we hope that with our continuing support, this research will eventually lead to novel and effective treatments for both brain and other cancers where HOX gene over-expression is a clear therapeutic target.”

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Research

Brain cancer research backed by award

Dr Sharel Peisan E’s research into nanoscale electrochemistry of brain cancer cells has received the Springboard Award

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Pioneering brain cancer research has been backed by a new six-figure award, to support its ambition to advance diagnosis and treatments. 

Dr Sharel Peisan E, a chemistry lecturer at Teesside University, will examine the nanoscale electrochemistry of brain cancer cells.

Using a multifunctional nanoscale electrochemical imaging platform, Dr E will be able to take a closer look at brain tumour cells and their processes to gain a better understanding of their biology.

The technology uses tiny electrodes to gain an extremely close and detailed visualisation of the biology of living cells.

This research project, backed by an award of £100,000, aims to explore how brain cancer reacts to different therapies on a cellular level, which will be applied to improving or designing more effective treatments for cancer patients.

It will also be able to provide insight into other neurodegenerative diseases such as Alzheimer’s in much the same way.

Glioblastoma is one of the most devastating cancers, although its biology remains somewhat of a mystery in cancer research, with brain cancer cells being difficult to analyse using current methods of examination,” explained Dr E, who is based at Teesside University’s National Horizons Centre.

NHC National Horizons Centre

“My research will use advanced nanoscale imaging to provide a new view of the solid, liquid and gaseous processes, known as heterogeneous processes, on the cancer cells at the nanoscale, providing additional information on the glioblastoma biology which has previously been unattainable through microscopic techniques, allowing us to improve current diagnostics and treatments.”

Dr E won the grant from the Academy of Medical Sciences as part of the Springboard Award, which provides funding and career support for innovative bioscientists.

Teesside University’s National Horizons Centre, based at the Darlington campus, is a £22.3million centre of excellence for innovation and training in biosciences and healthcare, with strength in cancer research.

Professor Vikki Rand, interim director of the National Horizons Centre, said: “Here at the National Horizons Centre, we are positioned at the forefront of the biosciences and healthcare sector, leading groundbreaking research to drive progress in key areas including disease and climate change.

“We are devoted to gaining as much knowledge about cancer as we can, and our work in cancer research is particularly impressive, directly influencing the wider healthcare sector through studies which inform new and improved therapies to help real patients which is, after all, what our research is all about.

“Grants such as the Springboard Award from the Academy of Medical Sciences are extremely important and we are thrilled that Dr E has won this very substantial funding for her research.”

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Research

Research could pioneer new brain haemorrhage treatment

The study could yield a breakthrough to reduce the risk of brain damage and disability and increase patients’ chances of survival

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A novel method is being pioneered for the treatment of brain haemorrhage, which it is hoped could reduce the risk of brain damage and disability and increase patients’ chances of survival.

Brain haemorrhages, or haemorrhagic strokes, occur when blood leaks from a blood vessel in or around the brain and in the UK accounts for about 15 per cent of all strokes.

The reaction of the brain to the sudden presence of excess blood can lead to brain damage, disability and death – with almost a half of patients going on to die within a month as a result of suffering a brain haemorrhage.

Researchers at Nottingham Trent University are now collaborating with the University of Manchester to find a way to prevent the damage to brain cells caused by iron from the blood that builds up in the brain after a haemorrhage.

“The death rates due to brain haemorrhage have not changed for several decades. This sort of research is therefore vital to find the new treatments necessary to improve survival,” said Professor Stuart Allan of the University of Manchester. 

The researchers – funded by Brain Research UK – are focusing on drugs called ‘iron chelators’, which bind to iron to prevent its accumulation in the body.

They will package these iron chelator drugs into bubbles (‘liposomes’) which can be used to more effectively deliver drugs into the body.

It can be challenging to target drugs to affected areas of the brain due to the ‘blood brain barrier’, which works to prevent potentially harmful toxins in the body from reaching it.

But the team hopes its novel approach will enable the drug to stay in the blood stream for a longer period of time and allow enough drug to get to the area of the brain that contains the bleeding, while also not exposing the rest of the body to unnecessary side effects.

The work, which will involve the use of mice and patient samples, will take about three years.

The study involves a multidisciplinary team of scientists led by Nottingham Trent University’s Dr Zahraa Al-Ahmady, in collaboration with Prof Stuart Allan, Dr Adrian-Parry Jones and Dr Ben Dickie at the University of Manchester and NTU’s Prof Sergio Rutella and Prof Graham Ball.

“Unfortunately, no specific medications currently exist to prevent or treat brain haemorrhage,” said lead researcher Dr Al-Ahmady.

“There are severe issues related to having this blood and iron accumulation in the brain, which contributes to the death of brain cells. 

“We hope our approach will prevent this excess iron from damaging neurons and other tissue and be a new approach to blocking blood induced brain damage after bleeding.

“Many of those who suffer a brain haemorrhage will sadly die and those who survive can have permanent disabilities and so the creation of new drugs is essential. 

“We are aiming to find a way to enable treatment to better infiltrate the brain and to remain at the disease site for longer before more serious damage occurs.”

Caroline Blakely, chief executive of Brain Research UK, said: “We’re excited to be funding this important work by Dr Al-Ahmady and collaborators, and hope that it will prove to be an important step towards improving outcomes for patients who have suffered a brain haemorrhage.

“We are only able to fund research like this thanks to the extraordinary efforts of our supporters, many of whom are raising funds in tribute to loved ones affected by brain conditions.”

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