A team of investigators at the University of Cincinnati (UC) report the development of a first-of-its-kind animal model that sheds light on an overlooked brain organ’s role in repairing the brain after a stroke.
The organ, called the choroid plexus, is found within brain ventricles that produce the brain’s cerebrospinal fluid (CSF), which circulates throughout the brain carrying signaling molecules and other factors important for brain function. Until now, little has been known about the roles played by both the choroid plexus and CSF in brain repair due to a lack of adult animal models. Details of the new model developed at UC are published in the Proceedings of the National Academy of Science.
“We have discovered a new use of an animal model to be able to allow us to manipulate the adult choroid plexus and CSF for the first time,” said Agnes (Yu) Luo, PhD, corresponding author on the study, and professor and vice chair in the department of molecular and cellular biosciences in UC’s College of Medicine. “Now that we’ve discovered it, this will be vitally applicable to allow researchers to manipulate the adult choroid plexus and CSF to study different disease models and biological processes.”
Importantly, the model allows researchers to examine neurogenesis, the process of the human brain that makes it capable of repairing brain damage by redirecting neurons to the lesion site in the brain following a stroke. But, as USC graduate student and study co-author Aleksandr Taranov noted, it remains unknown what regulates neurogenesis or how to direct neurons to the lesion site.
In their research, the UC investigators found that when they removed the choroid plexus, which resulted in the loss of CSF in brain ventricles, there was a reduction in the creation of neuroblasts or immature neurons. In an ischemic stroke model the team further found that the loss of the choroid plexus led to fewer neuroblasts migrating to the lesion site to repair the damage there.
“This suggests that the choroid plexus may be needed to retain these neuroblasts in the area where they usually reside,” Taranov said. “And the choroid plexus might actually be required to retain the neuroblasts so they can readily migrate into the stroke site whenever a stroke or other injury occurs.”
The research also suggests that the choroid plexus helps maintain a ready supply of regenerative cells that are ready to be deployed to injured areas of the brain in the animal model of stroke. Luo said that further research is now needed to see if this is also the case in human brains.
Armed with a working model of the choroid plexus, the UC team now intends to broaden their research to develop a deeper understanding of its function within the brain. Taranov has broaden his research into how it and the CSF affect the clearing of toxic proteins in an Alzheimer’s disease model. His colleague Elliot Wegman is studying the same effects in a model of Parkinson’s disease.
