How do extended space missions affect the brain?

By Cindy Abole

NASA astronauts have experienced altered vision and increased intracranial pressure (VIIP) during flight aboard the International Space Station. The VIIP syndrome is thought to result from the redistribution of body fluid toward the head during long-term microgravity exposure; however, the exact cause is unknown.

In the November 2, 2017, issue of the New England Journal of Medicine (doi: 10.1056/NEJMoa1705129), Donna R. Roberts, M.D., associate professor in the Department of Radiology and Radiological Sciences, reported the findings of a study comparing brain MRI scans from NASA’s Lifetime Surveillance of Astronaut Health program for two groups of astronauts: 16 astronauts who had been in space short-term aboard the space shuttle and 18 astronauts who had been in space for longer periods of time, typically three months, aboard the International Space Station.

Roberts’ team evaluated the cerebrospinal fluid (CSF) spaces at the top of the brain and CSF-filled structures, called ventricles, located at the center of the brain. The team also paired the preflight and postflight MRI cine clips from high-resolution 3-D imaging of 12 astronauts from long-duration flights and six astronauts from short-duration flights and looked for any displacement in brain structure.

Study results confirmed a narrowing of the brain’s central sulcus, a groove in the cortex near the top of the brain that separates the parietal and frontal lobes, in 94 percent of long-duration flight astronauts and 18.8 percent of the short-duration flight astronauts. Among the long-duration flight astronauts only, cine clips also showed an upward shift of the brain and narrowing of the CSF spaces at the top of the brain.

These findings suggest that significant changes in brain structure occur during long-duration space flight and that symptoms of VIIP syndrome would be expected to worsen the longer an astronaut stays in space. The parts of the brain that are most affected — the frontal and parietal lobes — control movement of the body and higher executive function.

With NASA’s Mars expedition mission set to launch in 2033, it is urgent for researchers such as Roberts to continue to collect data about astronauts and understand the basics of human space physiology.

Modeling pressure-induced cellular injuries in the brain

Elevated intracranial pressure (ICP), present in almost every category of brain injury, causes cellular injuries and additional neurological deficits beyond the initial insult. Yet little is known about ICP-mediated effects on cellular functions and the mechanism by which ICP-induced injuries occur, in large part because methods to study them have been lacking.

A team of investigators led by Ramin Eskandari, M.D., director of pediatric neurosurgery at MUSC Children’s Health, has developed an ex vivo model of ICP-induced cellular injury for understanding early cell-injury mechanisms and identifying biomarkers associated with pathological pressure in multiple brain injury etiologies. Eskandari’s group reported their findings in the January 1, 2018 Journal of Neuroscience Methods (doi: 10.1016/j.jneumeth.2017.10.004).

“The novelty of this model is we are able to simulate elevated ICP and examine this influence on nervous system cells suspended in a 3D matrix, which attempts to recapitulate early-injury scenarios to brain parenchyma not easily assessed in the clinical setting,” said Michael E. Smith, Ph.D., assistant professor of neurosurgery at MUSC and first author on the article.

The ex vivo system devised by Smith and Eskandari, called the Pressure-Controlled Cell Culture Incubator (PC3I), consists of separate acrylic chambers inside a cell culture incubator under a regulated and adjustable pressure. The originality of this ex vivo system is the ability to expose a 3D matrix of brain cells to extended periods of sustained as well as pulsatile pressure conditions while having complete control over all other parameters of the cell culture system. This allows for systematic and reproducible assessments of pressure effects at the cellular level. —Nouhou Ibrahim

Targeting pediatric brain cancer

Juvenile pilocytic astrocytoma (JPA), while rare, is the most common pediatric brain tumor. This type of tumor develops in astrocytes — star-shaped cells that surround and protect nerve cells— and is often benign and slow growing.

Research into this type of tumor is difficult due to the lack of an established cell line. Ramin Eskandari, M.D., director of pediatric neurosurgery at MUSC Children’s Health, and his team have solved this problem. In 2016, Eskandari removed a brain tumor from five-year-old Mary Scott Gallus. He then received permission from Mary Scott’s parents to use the resected tumor for research.

Eskandari gave part of the tumor to Arabinda Das, Ph.D., assistant professor in the Department of Neurosurgery. Das was able to purify and culture this low-grade tumor — the first-reported cell line for JPA. They named this brand new cell line MSG after Mary Scott Gallus.

Eskandari’s group also works on high-grade tumors and has developed a novel experimental treatment model targeting pediatric medulloblastoma that is detailed in the March 2017 Child’s Nervous System (doi: 10.1007/s00381-016-3305-x). When low-dose X-ray radiation was combined with immunotherapy (targeting HER2 or VEGF), T-cell-mediated cell death improved.

High-grade tumors are notorious for evading the body’s immune system. To combat this, Eskandari’s new treatment model uses a two-pronged approach. The first prong uses low-dose radiation that doesn’t kill tumor or brain cells; however, it shocks the immune system into recognizing the tumor as a foreign object. The second prong uses antibodies targeting proteins on the cell surface to enhance the immune cells’ ability to recognize the tumor. These in vitro results are tantalizing and warrant further investigation.
—Matthew Greseth