Abstract
The purpose of this mini-review is to examine if publicly available cerebrospinal fluid (CSF) proteomics data sets can be exploited to provide insight into the etiology of hydrocephalus, into the character of the injury inflicted on the parenchyma by ventriculomegaly, and into the response of the brain to this condition. While this undertaking was instigated by reanalysis of recent comparative proteomics of CSF collected from the brain of healthy and Mpdz knockout (KO) mice (Yang et al. 2019), it is an opportunity to survey previously published CSF proteomics data sets to determine if they can be pooled together to that end. The overabundance of extracellular matrix (ECM) proteins, complement factors, and apolipoproteins in the CSF of Mpdz KO mice was taken to indicate that the hydrocephalic brain underwent ischemia, inflammation, and demyelination. The overabundance of five cytokine-binding proteins could be linked uniquely to insulin-like growth factor (IGF) secretion and signaling. The overabundance of two serpins, angiotensinogen and pigment epithelium-derived factor (PEDF) was considered as a biomarker of anti-angiogenic negative-feedback mechanisms to reduce CSF production. These findings raise the intriguing propositions that CSF proteomics can identify biomarkers of case-specific injuries, and that IGF signaling and angiogenesis pathways can serve as therapeutic targets. It appears, however, that the currently available proteomics data is not amenable to comparison of CSF from normal and hydrocephalic patients and cannot be used test the premise of those propositions.
Highlights
Hydrocephalus is the most common cause of pediatric surgical intervention (Lim et al, 2018), occurring about once per 1,000 births in the US (Kahle et al, 2016)
We identified only three studies that had analyzed the CSF of hydrocephalus-harboring patients (Li et al, 2006; Scollato et al, 2010; Waybright et al, 2010)
The overabundant extracellular matrix (ECM) proteins, complement factors and apolipoproteins (Table 1), were associated with mechanisms of ventriculomegaly-inflicted injuries based on the following evidence: ECM1 was linked to neuroinflammation, whereby it ameliorated the demyelination caused by T helper cells (Su et al, 2016)
Summary
Hydrocephalus is the most common cause of pediatric surgical intervention (Lim et al, 2018), occurring about once per 1,000 births in the US (Kahle et al, 2016). Surgical treatment is palliative and does not address the underlying cause of hydrocephalus. These exigencies provide the rationale for the implementation of non-invasive approaches in place of or in support of invasive treatments. Shunt implantation facilitates sampling and analysis of the CSF for early detection of infection (Khalil et al, 2016). It could conceivably be analyzed for evaluating parenchymal health. Hydrocephalus Potential Therapeutic Targets proteomic analyses of human CSF to gauge their similarity and, the validity of drawing diagnostic and therapeutic inferences collectively by pooling all the available data
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