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Keeping blood free to flow

StokolEven in their mothers’ wombs unborn foals need proper blood flow to survive and grow. A clot cutting off blood to the wrong place can spell disaster or death.

That’s exactly what happens when the infectious disease equid herpes virus-1 (EHV-1) causes its infamous effects: abortions and adult neurological disease. Infected horses can form clots in blood vessels feeding the placenta or spinal cord. But how does the virus trigger these clots?

No one yet knows why horses with EHV-1 get clots, but clinical pathologist Dr. Tracy Stokol plans to find out and is looking at platelets (small cells in blood) as potential culprits. Platelets are involved in normal blood clotting, which stops bleeding after an injury. Following injuries, platelets start attaching to blood vessels, become activated, and stick together, helping a clot to form. But this same process that closes off wounds to stop blood flowing where it shouldn’t can also form clots that stop blood from flowing where it should.

“My theory is that EHV-1 is somehow activating platelets to start forming clots and encouraging them to grow,” said Dr. Stokol. “The question is how: is it through direct contact between the virus and platelets, indirect contact with virus-infected cells releasing fragments that turn platelets on, or some combination?”

Using flow cytometry, Dr. Stokol’s lab tested whether certain neurologic and abortion-causing strains of EHV-1 directly bind to and activate equine platelets. The project’s preliminary data suggest they do. Yet questions remain: how does EHV-1 activate platelets? Can we prevent this from happening? Can cells infected with EHV-1 activate platelets that haven’t been exposed to the virus?

A technique novel to veterinary medicine will also help Dr. Stokol determine whether platelets are activated by EHV-1-infected cells that make up the inner lining of blood vessels (endothelial cells). Using a microfluidic device her lab produced in 2010 with help from Cornell biomedical engineers, Dr. Stokol has grown a life-sized model one tenth of a millimeter thick that simulates real equine endothelium using living cells from a horse. By infecting the model endothelial cells with EHV-1 and infusing platelets over the cells, her lab can watch the platelets’ interactions with infected endothelium in real-time using digital video microscopy, then analyze the recordings.

“This device allows us to examine what’s happening in a life-like environment,” said Dr. Stokol. “If we can show platelets are the missing link bridging EHV-1 infections to the clots that cause EHV-1-related abortions and neuropathy, we’ll have found a new target for therapies. There are several commercially available platelet inhibitors, such as clopidogrel and aspirin, that could easily be tested for their ability to prevent platelet activation after EHV-1 infection. If effective, these medicines could potentially help change the outlook for infected horses and their young.”

Funded by the Zweig Memorial Fund for Equine Research