Tag: neurosurgery

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Different Brain Structures in Females Lead to More Severe Cognitive Deficits After Concussion Than Males

by Kelsey Geesler

Top: Axons in female and male subject brains Bottom: damaged axons in male and female brains after injury (Credit: Penn Medicine)

Important brain structures that are key for signaling in the brain are narrower and less dense in females, and more likely to be damaged by brain injuries, such as concussion. Long-term cognitive deficits occur when the signals between brain structures weaken due to the injury. The structural differences in male and female brains might explain why females are more prone to concussions and experience longer recovery from the injury than their male counterparts, according to a preclinical study led by the Perelman School of Medicine at the University of Pennsylvania, published this week in Acta Neuropathologica.

Each year, approximately 50 million individuals worldwide suffer a concussion, also referred to as mild traumatic brain injury (TBI). However, there is nothing “mild” about this condition for the more than 15 percent of individuals who suffer persisting cognitive dysfunction, which includes difficulty concentrating, learning and remembering new information, and making decisions.

Although males make up the majority of emergency department visits for concussion, this has been primarily attributed to their greater exposure to activities with a risk of head impacts compared to females. In contrast, it has recently been observed that female athletes have a higher rate of concussion and appear to have worse outcomes than their male counterparts participating in the same sport.

“Clinicians have observed for a long time that females suffer from concussion at higher rates than males in the same sports, and that they take longer to recover cognitive function, but couldn’t explain the underlying mechanisms of this phenomenon,” said senior author Douglas Smith, MD, a professor of Neurosurgery and director of Penn’s Center for Brain Injury and Repair. “The variances in brain structures of females and males not only illuminate why this disparity exists, but also exposes biomarkers, such as axon protein fragments, that can be measured in the blood to determine injury severity, monitor recovery, and eventually help identify and develop treatments that help patients repair these damaged structures and restore cognitive function.”

Read the full story in Penn Medicine News.

Douglas H. Smith is a member of the Penn Bioengineering Graduate Group.

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What Makes a Breakthrough? “Eight Steps Back” Before Making it to the Finish Lit

by Meagan Raeke

(From left to right) Breakthrough Prize recipients Drew Weissman, Virginia M-Y Lee, Katalin Karikó, and Carl June at a reception on Feb. 13. (Image: Courtesy of Penn Medicine News)

In popular culture, scientific discovery is often portrayed in “Eureka!” moments of sudden realization: a lightbulb moment, coming sometimes by accident. But in real life—and in Penn Medicine’s rich history as a scientific innovator for more than 250 years—scientific breakthroughs can never truly be distilled down to a single, “ah-ha” moment. They’re the result of years of hard work, perseverance, and determination to keep going, despite repeated, often discouraging, barriers and setbacks. 

“Research is [like taking], four, or six, or eight steps back, and then a little stumble forward,” said Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research. “You keep doing that over and over and somehow, rarely, you can get to the top of the step.” 

For Weissman and his research partner, Katalin Karikó, PhD, an adjunct professor of Neurosurgery, that persistence—documented in thousands of news stories across the globe—led to the mRNA technology that enabled two lifesaving COVID-19 vaccines, earning the duo numerous accolades, including the highest scientific honor, the 2023 Nobel Prize in Medicine. 

Weissman and Karikó were also the 2022 recipients of the Breakthrough Prize in Life Sciences, the world’s largest science awards, popularly known as the “Oscars of Science.” Founded in 2012 by a group of web and tech luminaries including Google co-founder Sergey Brin and Meta CEO Mark Zuckerberg, the Breakthrough Prizes recognize “the world’s top scientists working in the fundamental sciences—the disciplines that ask the biggest questions and find the deepest explanations.” With six total winners, including four from the Perelman School of Medicine (PSOM), Penn stands alongside Harvard and MIT as the institutions whose researchers have been honored with the most Breakthrough Prizes. 

Virginia M.–Y. Lee, PhD, the John H. Ware 3rd Professor in Alzheimer’s Research, was awarded the Prize in 2020 for discovering how different forms of misfolded proteins can move from cell to cell and lead to neurodegenerative disease progression. Carl June, MD, the Richard W. Vague Professor in Immunotherapy, is the most recent recipient and will be recognized at a star-studded red-carpet event in April for pioneering the development of CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.

The four PSOM Breakthrough Prize recipients were honored on Tuesday, Feb. 13, 2024, when a new large-scale installation was unveiled in the lobby of the Biomedical Research Building to celebrate each laurate and their life-changing discoveries. During a light-hearted panel discussion, the honorees shared how a clear purpose, dogged determination, and a good sense of humor enabled their momentum forward. 

Read the full story in Penn Medicine News.

Carl June and Jon Epstein are members of the Penn Bioengineering Graduate Group. Read more stories featuring them in the BE Blog here and here, respectively.

Weissman presented the Department of Bioengineering’s 2022 Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics.” Read more stories featuring Weissman in the BE Blog here.

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Could Psychedelics Simultaneously Treat Chronic Pain and Depression?

Ahmad Hammo

Ongoing clinical trials have demonstrated that psychedelics like psilocybin and LSD can have rapid and long-lived antidepressant and anti-anxiety effects. A related clinical problem is chronic pain, which is notoriously difficult to treat and often associated with depression and anxiety.

This summer, Ahmad Hammo, a rising third-year student in bioengineering in the School of Engineering and Applied Science, is conducting a pilot study to explore psilocybin’s potential as a therapy for chronic pain and the depression that often accompanies it.

“There’s a strong correlation between chronic pain and depression, so I’m looking at how a psychedelic might be used for treating both of these things simultaneously,” says Hammo, who is originally from Amman, Jordan.

Hammo is working under the guidance of neuroanesthesiologist and neuroscientist Joseph Cichon, an assistant professor in the Perelman School of Medicine. The effort is supported by the Penn Undergraduate Research Mentoring (PURM) program, administered by the Center for Undergraduate Research and Fellowships, which awards undergraduate students $5,000 to spend 10 weeks conducting research alongside Penn faculty.

Hammo’s project focuses on neuropathic pain, pain associated with nerve damage. Like other forms of chronic pain, most experts believe that chronic neuropathic pain is stored in the brain.

“Neuropathic pain can lead to a centralized pain syndrome where the pain is still being processed in the brain,” Cichon says. “It’s as if there’s a loop that keeps playing over and over again, and this chronic form is completely divorced from that initial injury.”

Read the full story in Penn Today.

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Konrad Kording on the Future of Brain-Computer Interfaces

Konrad Kording (Photo by Eric Sucar)

Though the technology for brain-computer interfaces (or BCI’s) has existed for decades, recent strides have been made to create BCI devices which are safer, smaller, and more effective. Konrad Kording, Nathan Francis Mossell University Professor in Bioengineering, Neuroscience, and Computer and Information Science, helps to elucidate the potential future of this technology in a recent feature in Wired. In the article, he discusses the “invasive” aspects of previous BCI technology, in contrast to recent innovations, such as a new device by Synchron, which do not require surgery and are consequently much less risky:

“The device, called a Stentrode, has a mesh-like design and is about the length of a AAA battery. It is implanted endovascularly, meaning it’s placed into a blood vessel in the brain, in the region known as the motor cortex, which controls movement. Insertion involves cutting into the jugular vein in the neck, snaking a catheter in, and feeding the device through it all the way up into the brain, where, when the catheter is removed, it opens up like a flower and nestles itself into the blood vessel’s wall. Most neurosurgeons are already up to speed on the basic approach required to put it in, which reduces a high-risk surgery to a procedure that could send the patient home the very same day. ‘And that is the big innovation,” Kording says.

Read “The Age of Brain-Computer Interfaces Is on the Horizon” in Wired.

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BE Seminar: “Neural Engineering and the Primate Brain: Working at the Electrical and Optical Interface” (Bijan Pesaran)

Our final Penn Bioengineering seminar of the fall semester will take place this Thursday. Keep an eye on the BE events calendar for upcoming spring seminars.

Speaker: Bijan Pesaran, Ph.D.
Professor
Neural Science
New York University

Date: Thursday, December 16, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link
Room: Moore 216

Abstract: Neural engineering is enjoying an era of transformative growth. Classical methods that dominated the neurosciences for decades are being replaced by powerful new technologies. In this talk, I will discuss how to engineer electrical and optical interfaces to the primate brain. I will first present work on electrode interfaces that stimulate and record at the surface of and within the brain. I will show how simultaneously measuring and manipulating neurons immediately beneath electrode contacts during behavior delivers ground-truth data. The results have implications for electrode interface design and new generations of implantable biomedical devices. I will then turn to optical neural interfaces. Two-photon fluorescence microscopy images the activity of neurons expressing genetically-encoded calcium indicators and is most often performed in small animal models, such as the mouse, worm and fly. I will present a cellular-resolution robotic imaging platform to investigate the non-human primate brain at scale. I will finish by discussing potential applications of this technology to a range of scientific and clinical goals.

Bijan Pesaran Bio: Bijan Pesaran is interested in understanding large-scale circuits in the primate brain and how to engineer novel brain-based therapies. Bijan completed his undergraduate degree in Physics at the University of Cambridge, UK. After a year in the Theoretical Physics department at Bell Labs Murray Hill, he went on to earn his PhD in Physics at the California Institute of Technology. He then made the switch to neuroscience as a postdoctoral fellow in Biology at Caltech. Bijan has been on the faculty at New York University since 2006. He is currently a Professor of Neural Science in the Center for Neural Science. In 2013, he was a CV Starr Visiting Scholar at the Princeton Neuroscience Institute at Princeton University. Among other honors and awards, Bijan has received a Burroughs-Wellcome Career Award in the Biomedical Sciences, a Sloan Research Fellowship, a McKnight Scholar Award, the National Science Foundation CAREER Award and is a member of the Simons Collaboration for the Global Brain.

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Penn Bioengineers Develop Implantable Living Electrodes

Living Electrode Panels (image courtesy of the Cullen Lab)

Connecting the human brain to electrical devices is a long-standing goal of neuroscientists, bioengineers, and clinicians, with applications ranging from deep brain stimulation (DBS) to treat Parkinson’s disease to more futuristic endeavors such as Elon Musk’s NeuraLink initiative to record and translate brain activity. However, these approaches currently rely on using implantable metallic electrodes that inherently provoke a lasting immune response due to their non-biological nature, generally complicating the reliability and stability of these interfaces over time. To address these challenges, D. Kacy Cullen, Associate Professor in Neurosurgery and Bioengineering, and Dayo Adewole, a doctoral candidate in Bioengineering, worked with a multi-disciplinary team of collaborators to develop the first “living electrodes” as an implantable, biological bridge between the brain and external devices. In a recent article published in Science Advances, the team demonstrated the fabrication of hair-like microtissue comprised of living neuronal networks and bundled tracts of axons — the signal sending fibers of the nervous system — protected within soft hydrogel cylinders. They showed that these axon-based living electrodes could be fully controlled and monitored with light — thus eliminating the need for electrical contact — and are capable of surviving and forming synapses with the brain as demonstrated in an adult rat model. While further advancements are necessary prior to clinical use, the current findings provide the foundation for a new class of “living electrodes” as a biological intermediary between humans and devices capable of leveraging natural mechanisms to potentially provide a stable interface for clinical applications.

Cullen has a primary appointment in the Department of Neurosurgery in the Perelman School of Medicine, with a secondary appointment in the Department of Bioengineering in the School of Engineering and Applied Science, and an appointment in the Corporal Michael J. Crescenz VA Medical Center in Philadelphia.

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Yale Cohen and Douglas Smith Awarded 2020 Penn Medicine Awards of Excellence

Yale Cohen, Ph.D.

Douglas H. Smith, M.D.

The Perelman School of Medicine has announced the winners of the 2020 Penn Medicine Awards of Excellence. The Office of the Dean says:

“These awardees exemplify our profession’s highest values of scholarship, teaching, innovation, commitment to service, leadership, professionalism and dedication to patient care. They epitomize the preeminence and impact we all strive to achieve. The awardees range from those at the beginning of their highly promising careers to those whose distinguished work has spanned decades.

Each recipient was chosen by a committee of distinguished faculty from the Perelman School of Medicine or the University of Pennsylvania. The contributions of these clinicians and scientists exemplify the outstanding quality of patient care, mentoring, research, and teaching of our world-class faculty.”

Two faculty members affiliated with Penn Bioengineering are among this year’s recipients.

Yale Cohen, PhD, Professor of Otorhinolaryngology with secondary appointments in Neuroscience and Bioengineering, is the recipient of the Jane M. Glick Graduate Student Teaching Award. Cohen is an alumnus of the Penn Bioengineering doctoral program and is currently the department’s Graduate Chair.

“Dr. Cohen’s commitment to educating and training the next generation of scientists exemplifies the type of scientist and educator that Jane Glick represented. His students value his highly engaging and supportive approach to teaching, praising his enthusiasm, energy, honesty, and compassion.”

Douglas H. Smith, MD, Robert A. Groff Endowed Professor of Research and Teaching in Neurosurgery and member of the Penn Bioengineering Graduate Group, is the recipient of this year’s William Osler Patient Oriented Research Award:

“Dr. Smith is the foremost authority on diffuse axonal injury (DAI) as the unifying hypothesis behind the short- and long-term consequences of concussion.  After realizing early in his career that concussion, or mild traumatic brain injury (TBI), was a much more serious event than broadly appreciated, Dr. Smith and his team have used computer biomechanical modeling, in vitro and in vivo testing in parallel with seminal human studies to elucidate mechanisms of concussion.”

Read the full story in Penn Medicine Communications.

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Penn Launches Region’s First Center for Translational Neuromodulation

Penn’s brainSTIM center will study neuromodulation to repair and enhance human brain function

Penn Medicine has launched a new center to study the brain, one of the most complex systems in the body:

The Penn Brain Science, Translation, Innovation, and Modulation (brainSTIM) Center brings together a team of leading neuroscientists, neurologists, psychiatrists, psychologists, and engineers at Penn using neuromodulation techniques to research, repair, and enhance human brain function—the first translational center of its kind in the region.

Among the key faculty involved in this new center is J. Peter Skirkanich Professor of Bioengineering Danielle Bassett. Bassett’s Complex Systems Lab studies biological, physical, and social systems by using and developing tools from network science and complex systems theory. Bassett, along with Assistant Professor of Psychiatry Desmond Oathes, will work to:

understand how TMS [i.e. transcranial magnetic stimulation] might improve working memory in healthy adults and those with ADHD by combining network control theory (a set of concepts and principles employed in engineering), magnetic stimulation of the brain, and functional brain imaging.

Read more at Penn Medicine News.