Dysregulation of cerebral blood flow as a major factor of cognitive decline in astronauts - Tamara Gruslova
Abstract
In the 21st century, efforts to explore space are intensifying more than ever before, with the main goal being travel to Mars. However, this requires longer spaceflight with consequently increased challenges to astronaut health including cognitive decline. Cognitive performance is highly important to mission success as astronauts must be at their best thinking capacity to effectively and independently solve problems. Studies on Earth show a correlation between cerebral blood flow (CBF) dysregulation and neurodegenerative diseases. Since CBF regulation is a result of neuronal demands, persistent changes would result in long term effects including cognitive decline. Normally, CBF regulation involves the neurovascular unit and a precise balance of vasoactive molecules. Human and animal data from microgravity illustrate a change in CBF due to factors such as the cephalad fluid shift and vascular stiffening. Uncovering the specific pathways involved will draw the Mars mission closer to reality.
Introduction
Humans have been enthralled by the idea of existence beyond Earth from the beginning of time. And after great efforts carried out by them, there has been more than half a century of
successfully manned space flight (Dunbar, 2020). However, the never-ending quest for
knowledge continues and the next frontier is deeper exploration of space through long duration flights. Since the first missions to space, humans have accumulated a vast amount of knowledge and at the same time recognized that space is a harsh environment. Spaceflight is known to elicit numerous changes to astronaut health including bone density loss, inflammation, muscle atrophy, and just as importantly cognitive decline (Garrett-Bakelman et al., 2019; Roberts et al., 2019). During spaceflight, astronauts must attain high cognitive performance and act upon large amounts of information. Thereby, cognitive decline would diminish the astronauts’ ability to successfully complete a mission. Further, this issue becomes increasingly critical in the case of long duration flights, such as those planned to Mars, as this requires astronauts to be prepared to make emergency decisions without the ability to consult Earth based experts.
Cerebral Blood Flow and Cognitive Decline
Recently, NASA’s twin study, in which one twin on Earth was compared with the other in space, multidimensionally studied the impact of long-duration spaceflight on human health.
Furthermore, along with other changes that occur in space, this study showed a decrease in
processing speed and spatial awareness (Garrett-Bakelman et al., 2019). Moreover, other work with brain MRIs has confirmed that widespread brain structural changes in astronauts are accompanied by cognitive decline during extended missions (Roberts et al., 2019).
There are many factors that may be involved in this impaired cognition; however, cerebral blood flow (CBF) dysregulation is one of the major influences. Studies on Earth have shown that CBF dysregulation is linked with the onset of neurodegenerative diseases and cognitive decline (Kisler et al., 2017). For example, patients with dementia demonstrate CBF to be lower than that of healthy individuals (Leeuwis et al., 2018). This is because much of CBF regulation is due to neuronal demands meaning persistent CBF alterations would cause damage to neurons and lead to long-term effects like cognitive decline.
Cerebral Blood Flow Control
In order to ensure sufficient perfusion and nutrient supply to the brain, CBF is controlled by two mechanisms, cerebral autoregulation and neurovascular coupling. Cerebral autoregulation is responsible for maintaining constant oxygen delivery despite changes in blood pressure, while neurovascular coupling provides rapid increases in blood flow to activated neurons (Azevedo et al., 2007). Normally, the neurovascular unit is responsible for regulating these two mechanisms. This unit is composed primarily of neurons, astrocytes, endothelial cells, and pericytes.
Figure 1. Diagram of the components forming the neurovascular unit.
However, the main cell types are undoubtedly astrocytes and endothelial cells (Muoio et al.,
2014). Astrocytes are the most abundant cell type in the brain and are central for neuron survival and regulation of CBF. Their endfeet in particular communicate directly with vascular
endothelial cells by releasing vasoactive molecules that change blood pressure (Attwell et al., 2019; Hort et al., 2019; Verkhratsky & Nedergaard, 2018). Astrocytes have recently also been found to have a great importance in other processes such as learning and memory, however, little is still known about their specific impact on cognition (Halassa & Haydon, 2019; Suzuki et al., 2011). Likewise, endothelial cells form the blood vessel lumen and also regulate blood flow by interacting with astrocytes and releasing vasoactive molecules.
Based on current models of neurovascular coupling, several overlapping control loops ensure the fine-tuning and adjustment of local CBF. These processes are complex and require a precise balance of interactions in each level of the reaction cascade (Hosford & Gourine, 2019). Further, there are many molecules involved in the regulation of vascular tone; however, the most prominent are nitric oxide, epoxyeicosatrienoic acid, and prostaglandin E2 (Filosa & Iddings, 2013).
Evidence of Cerebral Blood Flow Changes in Space
Space presents a unique environment were multiple factors can interact. One of these is
microgravity with the most immediately visible symptom being the cephalad fluid shift leading to a swollen face and ‘chicken legs’ in astronauts. This occurs as the gravity which usually pulls blood down to the lower extremities is not present causing a shift of fluid upward. In turn, this fluid accumulates causing blood vessels to dilate and CBF to increase (Michael, 2018; Nelson et al., 2014).
Figure 2. Illustration of the fluid distribution on Earth versus in space.
Also, as an effort to counteract the effects of this fluid shift several physical changes in the
cerebral vasculature occur, including stiffening and decreased elasticity (Prisby et al, 2006).
These combined influences on the vasculature result in the change in CBF seen during
spaceflight (Blaber et al, 2013). These effects have likewise been confirmed by experiments in small animals on the International Space Station. For example, observations of shuttle flown mice suggest that the space environment produces an increase in CBF (Taylor et al., 2013). Knowing that space induced CBF dysregulation occurs, it can be extrapolated that this causes the cognitive decline seen in space based on Earth studies proving a link between cognitive decline and CBF dysregulation.
Conclusion
Cognitive performance in astronauts is a critical aspect of space exploration. Current data shows a link between CBF dysregulation and cognitive impairment. However, even with this known connection, little is understood about the specific molecular and cellular pathways of how long duration spaceflight elicits changes to blood flow in the brain. Therefore, carrying out studies that determine these pathways will ultimately allow for preventative measures to hinder the onset of cognitive decline in turn permitting longer missions.
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