On March 14, 2013, HA posted a blog about the research of Dr. Sonia Podvin entitled, Research UPDATE: Investigating Alternative Treatment Options for Hydrocephalus. Angela, a member from our community, asked the following question: My son had hydrocephalus at birth due to aqueductal stenosis (AS). Would patients like this be a candidate?
In today’s blog, Dr. Podvin responds to Angela’s question:
Angela brings up a great question! Thanks for asking this. My advisers and I have wondered recently about the possible role of augurin in aqueductal stenosis resolution. I hope I can explain our hypothesis in a concise manner, which I always have trouble doing because I get excited about our project and get side tracked talking about it.
We have found in our work so far that there is less augurin secreted into CSF in the injured brain (see reference 1 below) and this permits more cells to grow in the tissue lining the ventricles, subventricular zone (SVZ) (see reference 2 below). A hypothesis that we are putting together with these findings in mind is if a young baby has a stroke or a brain injury, augurin will cease to be secreted into CSF where it would normally reach target cells lining the brain ventricles. This will allow cells to proliferate thickening the the ventricle lining a bit, and in the very narrow passage of the aqueducts, obstructing CSF flow. We think that decreased augurin is normally a desirable injury response following brain injury because its target SVZ cells happen to be stem cells that proliferate and migrate to the injured site for repair. However, in very narrow ventricle regions there is a possibility that proliferation might cause an obstruction.
If we can develop augurin-based therapeutics, we hope they might be able to resolve AS. Since hydrocephalus is a chronic brain injury and thus secreted augurin levels might be chronically lower in hydrocephalus (this is a key question and we are hoping to address it very soon!), administration of augurin or molecules like it could potentially reduce this thickening. If we can show this is true in animal models this would be a huge finding that it might work in hydrocephalus patients!
I hope this makes sense. We’ll put on our thinking caps for more possibilities in AS. Thanks for the question!
Dr. Sonia Podvin
Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury. Podvin S, Gonzalez AM, Miller MC, Dang X, Botfield H, Donahue JE, Kurabi A, Boissaud-Cooke M, Rossi R, Leadbeater WE, Johanson CE, Coimbra R, Stopa EG, Eliceiri BP, Baird A. PLoS One. 2011;6(9):e24609. doi: 10.1371/journal.pone.0024609. Epub 2011 Sep 14.
Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury. Gonzalez AM, Podvin S, Lin SY, Miller MC, Botfield H, Leadbeater WE, Roberton A, Dang X, Knowling SE, Cardenas-Galindo E, Donahue JE, Stopa EG, Johanson CE, Coimbra R, Eliceiri BP, Baird A. Fluids Barriers CNS. 2011 Jan 18;8(1):6. doi: 10.1186/2045-8118-8-6.