Gravitational Transitions Increase Blood-brain Barrier Permeability In Humans

Abstract

Scientific Abstract While spaceflight-associated neuro-ocular syndrome (SANS) related to intracranial hypertension (IH) is considered NASA’s top health risk for long-duration spaceflight, the underlying mechanisms remain unclear. PURPOSE: To examine if repeated bouts of micro- and hypergravity during parabolic flight (PF) would increase blood-brain barrier (BBB) permeability subsequent to the combined effects of cerebral hyper-perfusion (hemodynamic) and systemic oxidative-nitrosative (molecular) stress. METHODS: Six participants (5♂, 1♀) aged 29 ± 11 years were examined before, during and after PF. Six gender and age- matched (27 ± 6 years) controls were subject to the same procedures/experimental timeline with the exception of PF. Duplex ultrasound was employed to measure blood flow in the anterior (internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation, with venous blood assayed for biomarkers specific to oxidative-nitrosative stress (electron paramagnetic resonance spectroscopy/ozone-based chemiluminescence) and structural integrity of the neurovascular unit (NVU, chemiluminescence/ELISA). RESULTS: PF was associated with a selective increase in VA flow during the most marked gravitational transition from micro- to hypergravity (P < 0.05). Increases in oxidative-nitrosative stress, glio-vascular GFAP and S100ß were observed after PF (P > 0.05), the latter proportional to the increase in VA flow, whereas biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) remained stable (P > 0.05). CONCLUSION: Collectively, these data are the first to demonstrate that acute gravitational transitions result in minor BBB disruption due to the combined effects of hemodynamic-molecular stress thereby proposing an alternative candidate mechanism and biomarkers for the reported neurological sequelae underlying SANS.