A new international study led by the University of South Florida reports that the sugar alcohol compound mannitol improves the therapeutic effect of injecting human umbilical cord blood cells into a neonatal cerebral palsy rat model. Mannitol opens the blood brain barrier by temporarily contracting the tight endothelial cells that make up the blood brain barrier.
The research team believes that if blood cells can cross the blood brain barrier to reach the injured site, intravenous delivery of human umbilical cord blood (HUCB) may have a therapeutic effect on patients with cerebral palsy. Their findings were recently published online in the Journal of Cellular and Molecular Medicine (14:4).
There is supportive treatment for cerebral palsy, but it cannot be cured. Cerebral palsy is a group of neurological disorders caused by brain damage before birth or during infancy, characterized by impaired muscle coordination.
"The combination of mannitol and human umbilical cord blood therapy has increased the level of at least three neurotrophic factors in the central nervous system - neurotrophic factors derived from glial cell lines, nerve growth factors, and brain-derived neurotrophic factors," said Dr. Cesar Borlongan, the lead author of the study and professor of neurosurgery and brain repair at the University of South Florida School of Medicine
Dr. Borlongan and his co authors say that mannitol treatment cannot increase the survival rate of human umbilical cord blood (HUCB) grafts, but by improving the nutritional factors used in combination with HUBC and mannitol, "it can regulate powerful functional improvements.".
Dr. Borlongan commented, "In an animal model of neonatal cerebral palsy, intravenous infusion of human umbilical cord blood alone promotes behavioral recovery, but when human umbilical cord blood transplantation is combined with mannitol, its functional improvement is more pronounced."
He pointed out that experimental animals received various post-treatment exercise tests, and those receiving combination therapy instead of using HUCB alone or mannitol alone showed the greatest improvement in exercise.
"Our findings suggest that mannitol plays a key role in the permeability of the blood brain barrier," explained Dr. Borlongan.
Dr. Borlongan added that since newborn research animals receiving HUCB cells and mannitol combinations showed the strongest upregulation of neurotrophic factors, the study also showed that even immature blood brain barriers need to penetrate to promote the entry of HUCB and promote the role of neurotrophic factors. The long-standing view has been that young animals exhibit immature, incompletely developed blood brain barriers. However, researchers have demonstrated that controlling immature barriers still requires improving the pathway of therapeutic substances from the peripheral circulation into the brain.
"In addition, the therapeutic effect is achieved without immunosuppression, which often accompanies harmful side effects," Dr. Borlongan said.
Previous work by the research team has shown that in adult stroke model animals, transplanted cells do not need to cross the blood brain barrier to save the injured brain. In these studies, mannitol helps promote the entry of growth factors secreted by transplanted cells.
"Our current findings expand the usefulness of blood brain barrier infiltration in promoting cell therapy for neonatal brain injury and potential cerebral palsy," Dr. Borlongan concluded
The research team includes scientists from the Center for Excellence in Aging and Brain Repair at the University of South Florida, the Department of Neurology at the Georgia Medical School, the Saneron CCEL Treatment Company in Tampa, Florida, and the Cryopraxis ciob in Rio de Janeiro, Brazil.
