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Modeling pressure-induced cellular injuries in the brain 

By Nouhou Ibrahim


Schematic drawing of the Pressure-Controlled Cell Culture Incubator (PC3I)
The Pressure-Controlled Cell Culture Incubator (PC3I). Schematic drawing by Emma Vought.

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.