New research has shown that the window of opportunity for possible treatment for patients with traumatic brain injury (TBI) differs depending on whether the patient is male or female. Building on this, scientists from the University of Texas Health Science Center in Houston (UTHealth) and Arizona State University have embarked on a five-year, $ 2.5 million project sponsored by the National Institutes of Health (NIH).

The study will be used to help develop nanoparticle delivery systems that target both sexes for the treatment of TBI.

“Under normal circumstances, most drugs, even when encapsulated in nanoparticles, do not reach the brain in an effective concentration because of the blood-brain barrier. However, after a TBI, that barrier is compromised, giving us a window of opportunity to deliver these drugs to the brain, where they have a better chance of having a therapeutic effect, ”said Rachael Sirianni, PhD, Associate Professor of Neurosurgery at McGovern Medical school at UTHealth. Sirianni’s fellow and co-lead on this scholarship, Sarah Stabenfeldt, PhD, was the first to show that the blood-brain barrier timeframe differs between men and women, and it was this important finding that led them to apply for the NIH scholarship.

TBI is an acute force trauma that occurs on the head as a result of a fall or an object that hits the head with any force. The body responds with an acute response to the injury, followed by a chronic phase in which it tries to heal.

“In this second phase, various abnormal processes cause additional injuries that go well beyond the original physical damage to the brain,” said Sirianni.

Under normal circumstances, the blood vessels in the brain are very selective about what they allow to enter the brain, which helps protect it from substances that could damage neuron cells and create a very carefully controlled blood-brain barrier . During this second healing phase after TBI, however, these blood vessels are impaired and substances can penetrate.

One of the many factors that could cause this difference between female and male patients is different levels and cycles of sex hormones such as estrogen, progesterone, and testosterone. While these values ​​are already different in healthy people, brain injuries can also cause additional hormonal imbalances in both sexes.

Sirianni said this work is extremely important because there are currently no effective treatments for TBI. According to the Centers for Disease Control and Prevention (CDC), an estimated 1.5 million Americans develop TBI each year.

“The aim of this research is to develop different systems for the delivery of nanoparticles that can target the unique physiological state of men and women after TBI. Through this research, we hope to develop an optimal delivery system for these drugs that are delivered to the brain and hopefully find an effective treatment plan for TBI, ”said Sirianni.

Drugs previously considered unsafe or ineffective when administered systemically can instead be targeted directly to the microenvironment of the injury via nanoparticle delivery systems.

“With these nanoparticle systems, we are testing how we can rethink a drug that showed promise in preclinical or clinical studies but then failed,” said Stabenfeldt.


Adapted from a press release from Arizona State University


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