Proteomics of Cerebral Spinal Fluid (CSF) in Hydrocephalus Research – Dr. Anthony Avellino, Assistant Professor of Neurological Surgery at Seattle Children’s Hospital and Regional Medical Center and the University of Washington

The primary goals of Dr. Avellino’s research are:

1. Study the role of CSF proteomics in children with hydrocephalus and without hydrocephalus.
2. Gain a better understanding of pathological mechanisms and neurological sequelae of hydrocephalus.
3. Identify important factors affecting patient cognitive developmental outcome.

Most hydrocephalus-related research has been directed at studying what effect increased intracranial pressure, cerebral ischemia, hypoxia, physical disruption of axons and neurons, and changes in the extra cellular microenvironment have on hydrocephalus-induced brain injury. To our knowledge, the global protein composition in ventricular CSF from children with hydrocephalus has not been studied using ultrahigh resolution mass spectrometry techniques. In the past, researchers using 2-dimensional electrophoresis have identified less than 100 proteins in CSF. However, with the advent of high-resolution mass spectrometry techniques, we have the potential to identify thousands of CSF proteins. To our knowledge, the global protein composition in ventricular CSF from children with hydrocephalus has not been studied using mass spectrometry techniques.

CSF is an extremely important biofluid to study as it is distributed diffusely throughout the brain where it constantly bathes and cushions the brain. CSF is also an important and rapid route for molecular signal transfer between different brain regions. Thus, alterations in the protein composition of CSF may reflect abnormalities in protein expression associated with hydrocephalus as well as trauma, neurodegenerative disorders, multiple sclerosis, and idiopathic low-back pain.

In addition, altered CSF proteins in different hydrocephalus states may alter neuronal development and migration, stem cell proliferation, and neuronal and glial cell survival. Why cognitive developmental outcome is different in children with shunted hydrocephalus, even when the brain reconstitutes after shunting, is a critical question faced by many pediatric neurosurgeons, neurologists, and pediatricians. (Figure1).


Summary: to characterize the global CSF proteome in children with and without hydrocephalus which is critical to better understand the pathogenesis of hydrocephalus in relation to neuronal cell injury, survival, and development. Knowledge of known and/or unknown novel unregulated or downregulated proteins in children with hydrocephalus may
allow us to develop novel molecular and pharmacologic therapies which could decrease CSF production and/or increase CSF absorption to treat hydrocephalus, hopefully
without a ventricular shunt procedure; and, ultimately, improve neurologic and cognitive developmental outcome.



Definitions:

- Proteomics is a new science that focuses on the study of proteins : their roles, their structures, their localization, their interactions, and other factors (the study of proteins falls in the domain of chemistry).
- Sequelae – a pathological condition resulting from a disease or secondary consequence or result.