UConn School of Medicine researchers, in Experimental Neurology, demonstrated 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. 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 overactive, it causes a cascade of detrimental effects in brain cells, leading to ischemic brain injury.

In the study, the researchers suggest that 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 overstimulated immune response to improve both acute and chronic stroke recovery.

This method only operates during this period of overactivation and does not inhibit normal functions of P2X4R during long-term recovery, according to a media release from the University of Connecticut.

“Short-term P2X4R inhibition works perfectly to prevent brain damage immediately after stroke as well as during long-term recovery.”

— study author Rajkumar Verma, assistant professor of neuroscience at the UConn School of Medicine and the Pat and Jim Calhoun Cardiology Center at UConn Health

Intervention Studied in Mouse Models

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 overabundant.

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, the release continues.

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, the researchers add.

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

— Rajkumar Verma

[Source(s): University of Connecticut, EurekAlert]

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