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Medical News & Perspectives
Wild Health
September 4, 2019

Pigs Model Human Brains, Snake Fangs Inspire Microneedles, and Canines Advance Cardiac Imaging

JAMA. Published online September 4, 2019. doi:10.1001/jama.2019.12580

Wild Health offers an occasional look at the animal kingdom’s contributions to human health.

People with neurological disorders, an aversion to injections, and blood vessels that don’t supply their heart with adequate oxygen may benefit from recent animal research results.

Hoon-Eui Jeong, PhD/Ulsan National Institute of Science and Technology
Pigs and Humans Have Similar Brain Networks

Humans and pigs may have more in common than previously realized, and those similarities may help researchers develop methods to treat, prevent, or diagnose neurological disorders such as chronic traumatic encephalopathy (CTE) or Alzheimer disease.

In a recent Brain Connectivitystudy, researchers at the University of Georgia used resting-state functional magnetic resonance imaging and diffusion tensor imaging to examine functional connectivity in pigs’ brains. Their analysis of the imaging data showed that swine have 6 brain networks, commonly called resting-state networks, that resemble those in the human brain. The researchers found similarities between humans and pigs in the executive control, cerebellar, sensorimotor, visual, auditory, and default mode networks, which influence perception, feelings, movement, and memory.

Although swine have been considered useful in studying neurological diseases because of physiological and anatomical similarities to the human brain, the recent findings show the animals can be valuable as a model for studying functional connectivity in the brain. To date, no such model has been developed.

Interrupted brain connectivity is involved in neurological disorders such as CTE, Parkinson disease, Alzheimer disease, and autism. The investigators noted that traumatic brain injury damages the same brain networks in humans as it does in pigs.

Snake Fang Inspires Microneedle Design

From the mouths of rear-fanged snakes comes the development of a microneedle patch that may effectively deliver liquid drugs and vaccines merely by pressing it gently against the skin.

So what is it about rear-fanged snakes that makes them a good model for delivering liquid formulations transdermally? In a Science Translational Medicinestudy, researchers from the Republic of Korea and the United States explained that the reptiles’ fangs have an open groove on their surface. Venom from the Duvernoy gland behind the snake’s eye flows along the groove and into a prey animal as the fang penetrates its skin.

Unlike front-fanged snakes and hypodermic needles that employ high pressure to inject venom or medication through a hollow core, rear-fanged snakes release venom rapidly and efficiently without the need for a high-pressure delivery system. Despite rapid advances in microneedle technology, the researchers noted that a simple, universal microneedle patch platform that can deliver therapeutic liquids without bulky pumps, expensive microelectromechanical systems, or other adaptations isn’t yet available.

To emulate the rear-fanged snake’s grooved molar, the researchers designed a fingertip-sized microneedle patch with a reservoir to hold a liquid drug formulation and needles having multiple grooves to enhance the rate of drug delivery. The needles had 2 main parts—a tip without grooves to pierce the skin and a grooved wing to channel the liquid from the reservoir into the skin. Capillary action and surface tension enable the liquid’s movement.

When the researchers used the microneedle patch to deliver a fluorescently labeled protein, an anesthetic, and 2 types of vaccine in animals, they found that the liquids penetrated skin within seconds and gradually diffused into the skin. Comparisons with intramuscularly injected vaccine showed that delivery with the microneedle patch resulted in stronger immune responses with lower antigen concentrations—a dose-sparing effect. The researchers wrote that despite the need for further studies, their design could “provide a valuable platform for the simple, fast, and smart administration of diverse liquid drugs, biotherapeutic agents, and vaccines.”

The Heart’s Best Friend?

A canine model has helped researchers develop a method to detect deficits in myocardial oxygenation without using invasive intravenous contrast agents or ionizing radiation.

Abnormalities in myocardial oxygenation—the blood vessels’ ability to supply the heart with oxygen—play a major role in ischemic heart disease, the leading cause of death worldwide. Identifying an inadequate supply of oxygen to the heart muscle can help prevent potentially fatal events such as stroke or heart attack. But current methods used to assess myocardial oxygenation either aren’t reliable, use potentially harmful radioactive tracers, or require intravenously delivered contrast agents that are contraindicated for patients with chronic kidney disease.

“For these reasons, a noninvasive method of measuring myocardial oxygenation is preferable,” wrote the team of investigators from the United States, Canada, and the United Kingdom.

The investigators turned to a noninvasive imaging technique called blood oxygen level–dependent cardiac magnetic resonance imaging (BOLD-CMR) for a potential solution. Previous studies had shown that the technique can identify changes in myocardial oxygenation but that physiologic and imaging noise limited its ability to produce clear images of small changes in the heart.

To overcome those challenges, the investigators exposed healthy dogs and those with coronary stenosis to intermittently elevated arterial carbon dioxide levels, which triggered changes in myocardial blood flow that could be reliably detected by BOLD-CMR. To improve image resolution, they used BOLD signal averaging and developed a computational technique to reduce the noise from breathing, heart rate, and other types of physiologic motion.

Analyses showed that the approach could identify healthy myocardial tissue as well as regions affected by coronary stenosis with more than 90% sensitivity, specificity, and accuracy. “This has the potential to identify [ischemic heart disease] and a diverse spectrum of heart diseases related to myocardial ischemia,” the investigators wrote.