In this study, 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 cerebrum, 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).

The etiology of IIH is a topic of debate. The moderately elevated ICP over many years has been linked to cognition losses relieved by lumbar tapping to reduce ICP. While most cases are seen in overweight women of child-bearing age, there is no specific condition on Earth that shares more similarities to VIIP, constituting a reasonable analog to study the effects of chronically elevated ICP at the molecular level.

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 or RNAseq.

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. Both gene sets suggest that inflammatory processes are acting both locally in the brain as well as systemically, perhaps contributing to IIH pathophysiology.

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.

For a long time, the CNS has been considered a site of immune privilege, suffering from costly physiologic consequences if subject to inflammation due to trauma or infection. Further studies should be directed towards assessing the extent of these processes and their correlation with neurocognitive parameters.