Inhibition of key receptor implicated in post-stroke damage and recovery

NewsGuard 100/100 Score

Many people who suffer a stroke are permanently disabled. Stroke remains the leading cause of long-term disability in the United States. Paralysis of one side of the body, speech and language problems, vision problems and memory loss are some of the major consequences of stroke injury.

Every year, nearly 800,000 people in the United States have a stroke. Even with recent advances in treatments to reduce damage and enhance recovery after stroke, solutions are significantly lacking.

Recently, UConn School of Medicine researchers published a paper in Experimental Neurology showing how they successfully inhibited an important receptor implicated in post-stroke damage and recovery.

The researchers specifically looked at ischemic stroke, which comprises 87% of strokes. Ischemic stroke occurs when there is a blockage in an artery leading to the brain. This reduces the amount of blood and oxygen getting to the brain, causing damage or death of brain cells.

Damaged or dying brain cells release excessive amounts of stored adenosine triphosphate (ATP), a molecule that carries energy within cells, leading to over-stimulation of its receptor P2X4 (P2X4R). When P2X4R is over-active, it causes a cascade of detrimental effects in brain cells, leading to ischemic brain injury.

In this study, the researchers found inhibition of P2X4R can regulate the activation of a kind of immune cell that plays a large role in post-stroke inflammation.

By partially short-term blocking this receptor, the researchers limited the over-stimulated immune response to improve both acute and chronic stroke recovery.

The method presented in this paper is particularly attractive as it only operates during this period of over-activation and does not inhibit normal functions of P2X4R during long-term recovery.

"Short-term P2X4R inhibition works perfectly to prevent brain damage immediately after stroke as well as during long-term recovery," author Rajkumar Verma, assistant professor of neuroscience at the UConn School of Medicine and the Pat and Jim Calhoun Cardiology Center at UConn Health, says.

Using mouse models, the researchers observed improved balance and coordination, as well as reduced anxiety after their intervention.

The P2X4R inhibitor treatment decreased the total number of infiltrated leukocytes, which are white blood cells that promote ischemic injury when over abundant.

This treatment effectively reduced the cell surface expression and activation of P2X4R without reducing its total protein level in brain tissue after stroke injury.

One challenge many experimental drugs, including commercially available P2X4R inhibitors, face is insolubility, meaning they cannot enter the body in order to deliver the treatment.

The researchers are currently working with team members Dr. Bruce Liang, Dean of the UConn School of Medicine, and Kenneth Jacobson from the National Institutes of Health to develop more soluble and potent novel P2X4R inhibitors.

This technology would have a major impact as there is currently no effective drug to target stroke damage on the market aside from a few narrowly applicable treatment to dissolve blood clot or device to remove it.

From a drug perspective, we don't have anything for neuroprotection. It's a very big and open market."

Rajkumar Verma, Study Author and Assistant Professor, Department of Neuroscience, School of Medicine, University of Connecticut

With this successful demonstration of their proof of concept, the researchers will continue to refine this method to find the most effective inhibitors. The team is currently working with UConn Technology Commercialization Services to license this innovation. For more information, contact Ana Fidantsef, Ph.D.

Journal reference:

Srivastavaa, P., et al. (2020) Neuroprotective and neuro-rehabilitative effects of acute purinergic receptor P2X4 (P2X4R) blockade after ischemic stroke. Experimental Neurology.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Study reveals obesity's link to increased risk of multiple sclerosis and ischemic stroke