Inflammatory gene expression signatures in idiopathic intracranial hypertension: possible implications in microgravity-induced ICP elevation

Abstract

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. Gene expression signatures were obtained from exosomes collected from CSF and plasma in patients with possible signs of IIH. The gene expression targets focused on inflammatory genes and miRNAs. The results suggest that inflammatory cytokine-driven processes and immune cell migration are activated when ICP is elevated in IIH patients, either as a cause or effect of the ICP increase. Several miRNAs appear to be involved in this response, among which miR-9 and miR-16 are upregulated in CSF and plasma of higher ICP subjects. This study provides evidence in support of neurophysiological alterations and neuro-immunomodulation in this condition. If similar changes are seen in astronauts manifesting with the VIIP syndrome, an underlying pathophysiological basis may be discovered.

Conflict of interest statement

Dr Zanello is the recipient of the NASA award funding this study, as well as other research support from the agency. Dr Tadigotla is employed by Exosome Diagnostics, Inc. and holds stock options from Exosome Diagnostics. Dr James Hurley is employed by Exosome Diagnostics, Inc. and holds stock options from Exosome Diagnostics. Dr Skog is Chief Scientific Officer at Exosome Diagnostics, Inc. and holds stock options from Exosome Diagnostics. Mr Brian Stevens and Ms Eusebia Calvillo report no disclosures. Dr Bershad performs neurology clinical practice, and conducts several research projects funded by NASA and the NSBRI (National Space Biomedical Research Institute)

Figures

Fig. 1

Main miRNA and canonical pathways represented in patients with elevated ICP. miRNA Target Filter Analysis (Ingenuity Pathways Analysis, IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity) was applied to the differentially expressed gene data set from CSF (a) and plasma (b). miRNA and target relationships are shown by arrows, as well as the main possibly affected canonical pathways