Very premature infants are at high risk of developing post hemorrhagic hydrocephalus (PHH) as a complication to intraventricular hemorrhage (IVH). Most often these infants will need permanent ventricular shunting to regulate the cerebrospinal fluid (CSF) flow. However, shunting has a high rate of complication that frequently requires multiple revisions resulting in a child having multiple brain surgeries. For this reason, a therapeutic method to prevent PHH is crucial and highly desired. In a study published in Brain, researchers, investigate the potential of the molecule, decorin, in preventing PHH. The results are exciting and show great promise in the work to develop a preventive therapy for the development of hydrocephalus. Dr. James P. (Pat) McAllister, member of the Hydrocephalus Association (HA) Medical Advisory Board and an HA Experienced Investigator grant recipient, was one of the primary researchers in the study.
The study, “Decorin prevents the development of juvenile communicating hydrocephalus,” published in Brain, researchers working in mouse models found that continuous infusion of decorin, a naturally occurring protein that influences cellular functions, prevented the development of hydrocephalus after IVH.
Intraventricular hemorrhage, most frequently affecting premature infants, occurs when the small blood vessels along the ventricle lining rupture. During IVH, factors released can induce an inflammatory response and fibrosis, the thickening and scarring of connective tissue. This inflammation and scarring can contribute to the development of post hemorrhagic hydrocephalus by impairing CSF flow and reducing drainage. One such factor that can cause inflammation and scarring is the fibrogenic signaling molecule, transforming growth factor-β (TGF-β). TGF-β has been found to be in higher concentration in the CSF of hydrocephalus patients than in the CSF of normal controls, and thus has been implicated in the development of PHH. Decorin, a naturally occurring protein, has been reported to inhibit TGF-β activity, indirectly suppressing inflammatory scarring. In the current study, researchers found that decorin could prevent the development of hydrocephalus in a mouse model of juvenile communicating hydrocephalus.
For the study, rats were randomly assigned into one of four groups. The researchers found that the decorin treatment prevented ventricular enlargement so that the treatment group was indistinguishable to the intact or healthy group, indicating that the decorin prevented the development of hydrocephalus. The main findings of the study was that decorin reduced fibrosis in the subarachnoid space, suppressed the inflammatory response and protected against hydrocephalus-induced brain damage.
This study shows great promise in the development of potential therapies to prevent post hemorrhagic hydrocephalus. The treatment group was similar to the control group. More studies such as this are needed to find and develop new non-surgical treatments for hydrocephalus. HA would like to acknowledge Dr. McAllister and his colleagues on this incredibly valuable study.
The abstract can be found https://brain.oxfordjournals.org/content/136/9/2842.short