NIH-OHSU study: Short-term brain inflammation may help treat neurological tumors, disease

Edward Neuwelt, M.D., professor of Neurology and Neurological Surgery in the OHSU School of Medicine, stands in front of Mackenzie Hall on the OHSU campus.

New research, recently published in the Proceedings of the National Academy of Sciences,  has determined that activating neuroinflammation, via osmotic disruption of the blood-brain barrier, may benefit treatment of certain brain tumors.

The blood-brain barrier is a unique feature of blood vessels in the brain that blocks the passage of molecules from the blood into brain tissue. According to Edward Neuwelt, M.D., professor of Neurology and Neurological Surgery in the OHSU School of Medicine  and the Portland Veterans Affairs Medical Center, while the barrier helps to protect the brain, it also limits the delivery of therapies for treatment of neurological diseases and cancers.

By briefly opening, or disrupting, the blood-brain barrier, Neuwelt – who pioneered the technique more than 30 years ago – says that increased concentrations of chemotherapy, antibodies and nanoparticles are able reach a brain tumor in animal models more effectively.

The recent study, performed by OHSU in collaboration with scientists at the National Institute of Biomedical Imaging and Bioengineering and the  National Institutes of Health Clinical Center –  used a rat model to investigate molecular changes at the transcriptional and translational levels following blood-brain barrier disruption, or BBBD.  The group discovered that growth factors, cell adhesion molecules and cytokines, or small proteins important in cell signaling, increased within 5 minutes of BBBD, and  returned to normal rates within 96 hours.

“These changes occurred throughout the infused brain hemisphere, rather than very localized changes seen with other techniques to open the blood-brain barrier,” says Neuwelt. “Further, the increased inflammation had little toxicity to brain tissue or blood vessels, signaling that it could help to treat brain tumors and neurological diseases more effectively.”

While additional research is necessary, the research team believes this new finding helps to accelerate the potential for clinical application of BBBD to stimulate immune responses for targeted treatment of specific central nervous system diseases.

In addition to Neuwelt, study co-authors include: Scott Burks, Ph.D., Jaclyn Witko, Maggy Sundby, of the National Institutes of Health Clinical Center, Joseph Frank of the NIH Clinical Center and National Institute of Biomedical Imagine and Bioengineering, and Leslie Muldoon, Ph.D., Cymon Kersch, M.D., Ph.D., and Michael Pagel of the OHSU Department of Neurology.

This research was funded by the Intramural Research Programs of the Clinical Center and the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health, by NIH Grants CA199111 and CA137488, a Veterans Administration Merit Review Grant (BX003897), the Jonathan D. Lewis Foundation, and the Walter S. and Lucienne Driskill Foundation.

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