In the study, researchers assessed the visual impairment and intracranial pressure (VIIP) syndrome is a neuro-ophthalmologic condition described in astronauts returning from long-duration space missions. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is characterized by a chronic elevation of intracranial pressure (ICP) in the absence of an intracranial mass lesion.

Because VIIP and IIH share some neurologic and ophthalmologic manifestations, the latter might be used as a model to study some of the processes underlying VIIP. This work constitutes a preliminary investigation of the molecular pathways associated with the elevation of ICP in IIH.

Human space exploration involves multi-system health risks. Neuro-ophthalmologic symptoms, including elevated intracranial pressure (ICP) upon return to Earth, have been observed in astronauts participating in long-duration missions, a condition named visual impairment and intracranial pressure syndrome (VIIP).

On Earth, these neuroanatomical findings concur with those in idiopathic intracranial hypertension (IIH). A gene expression survey of exosomal RNA in CSF and plasma from patients with elevated ICP (>18 mmHg) compared to patients with normal to moderately elevated ICP (11–18 mmHg).

All subjects recruited for the study reported to the neurology clinic, therefore none represented a completely “healthy” volunteer and results need to consider the existence of underlying conditions. Although this study only examined a limited panel of mRNAs and miRNAs, it is expected that a similar proportion of overlapping genes would have been found with a wider expression screening, like whole genome microarray.

Despite the small overlap in the set of differentially expressed genes from CSF and plasma, the identified pathways associated with increased ICP were similar. Pro-inflammatory pathways such as acute phase response and interleukin signaling were highly represented.

Pathway analysis at the CSF level also suggested processes of brain cell death, possibly targeted by miR-9. This hypothesis is also supported by evidence that involves miRNA-9 in degenerative diseases, as well as promoting glial activation via the NFkB pathway Interestingly, miR-9 is itself targeted by miR-16, which was also observed to be upregulated in the high ICP group.

Circulating miRNAs are increasingly gaining attention as screening biomarkers in central nervous system (CNS) diseases. In this work, identified candidates warrant monitoring in larger cohort studies to investigate their biomarker value, i.e., miR-16, also investigated as a biomarker for glioblastoma, and CD86 (CD80), which has been implicated in progressive inflammatory myelopathy.

The study evaluates the molecular players in IIH and the first comparison between expression profiles from exosomes in CSF and plasma for this condition. Because elevation of ICP is a hallmark of the disease, findings from this study may be relevant to the VIIP syndrome.

The results from the CSF survey suggest neuro–immunomodulatory processes, and further work including astronauts exposed to microgravity and the concomitant fluid shifts with ICP increase, is proposed to test this hypothesis on a more relevant sample population.