Under Pressure: Novel technology to model pressure-induced cellular injuries in the brain

December 01, 2017

Hundreds of thousands of patients from newborns to the elderly are forced to grapple with the devastation of brain injury each year, and unlike many diseases where certain demographics are protected, brain injury can happen to anyone, anytime and anywhere. Elevated intracranial pressure (ICP), which is a byproduct of the rigid skull in which the brain resides, is the primary cause of initial injury. High ICP in turn causes cellular injuries in the brain and additional neurological deficits beyond those associated with the initial insult. Although substantial research has been done on brain injuries, most of it focuses on patient outcomes after the primary insult and does not explore the secondary cellular injuries caused by persistent elevation of ICP or the mechanisms that underlie them. As a result, little is known about those mechanisms.

Investigators at the Medical University of South Carolina (MUSC) have developed an ex vivo model of ICP-induced cellular injury that preliminary data suggest could be a useful tool for understanding early cell-injury mechanisms and identifying biomarkers associated with pathological pressure in multiple brain injury etiologies. They report their findings in an article published online on October 6, 2017 by the Journal of Neuroscience Methods.

"The novelty of this model is that there are very few examples in the literature where people have been able to put cells under pressure to see the effects," says Michael E. Smith, Ph.D., assistant professor of neurosurgery in the MUSC College of Medicine and first author on the article. "In patients with brain injury, the initial insult has already occurred and the clinician can only do so much to address that damage. Addressing the secondary ICP-induced effects could help minimize the neurological deficits sustained by the patient. We are interested in modeling ICP-induced secondary cellular injury to facilitate the development of such therapies."

The system, devised by Smith and Ramin Eskandari, M.D., director of pediatric neurosurgery at MUSC Children's Health and senior author on the article, is composed 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.

To experimentally test this system, Smith and Eskandari subjected astrocytes or neurons embedded in 3D hydrogels to a pressure of 30 cm H20 (22 mm Hg), which is considered pathological pressure, for various periods of time from a couple of hours to a couple of days. Adenosine triphosphate (ATP) release, which signals cellular stress and susceptibility to damage, was measured, as was the viability of the various cells once they were removed from pressure.

Under sustained pressure exposure, the ATP release was significantly higher in neurons compared with controls at 18 hours of exposure, while little effect was observed in astrocytes. Similarly, initial data demonstrate that neurons are more susceptible to pressure and, after a couple of days of pressure exposure, have a delayed but dramatic decrease in viability even when pressure is normalized. This novel model of elevated ICP successfully initiated cellular stress and did so in a cell-specific manner.

The model, developed to study pediatric hydrocephalus, could prove useful in elucidating mechanisms that are relevant to other types of brain injury, including brain tumors, stroke, subdural hematoma and traumatic brain injury.

"The ability to stop the deleterious downstream effects of brain injury diseases will allow clinicians to alter the recovery process in some of the most devastating diseases from which humans suffer," says Eskandari. "Developing that ability starts with a model system that is reliable and reproducible and can be easily altered to study many different diseases. We feel that we have created such a model and are excited to be finally demonstrating our results."
-end-
About MUSC

Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents in six colleges (Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing, and Pharmacy), and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion, with an annual economic impact of more than $3.8 billion and annual research funding in excess of $250 million. MUSC operates a 700-bed medical center, which includes a nationally recognized children's hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center), Level I trauma center, Institute of Psychiatry, and the state's only transplant center. In 2016, U.S. News & World Report named MUSC Health the number one hospital in South Carolina. For more information on academic programs or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.

Medical University of South Carolina

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.