Pulling the Plug on Brain Injury

Wednesday, November 15, 2023

Manipulating Fluid Flows Could Save Lives, Improve Recovery Post-TBI

Cerebral edema, the dangerous brain swelling that occurs after traumatic brain injury (TBI), can increase risk of death tenfold and significantly worsen prospects for recovery in brain function.  In extreme cases, surgeons will remove a portion of the skull to relieve pressure, but this has significant risks and is not viable for the vast majority of TBI cases. Physicians have very few tools at their disposal that are effective in treating cerebral edema, which is one of the leading causes of in-hospital deaths and is associated with long-term neurological disability.

New research appearing today in the journal Nature could change all that, showing that a cocktail of drugs already approved to treat high blood pressure quickly reduces brain swelling and improves outcomes in animal models of brain injury.

“Our research shows that cerebral edema is the consequence of impaired fluid flow through the glymphatic system and its associated lymphatic drainage,” said Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine and senior author of the study.  “This impairment is under adrenergic control, and can therefore be rescued pharmacologically by broadly inhibiting adrenergic receptors. Because these drugs are already being used clinically and have observed neurological benefits, there is the potential to move quickly to clinical studies to confirm these findings.”      

The glymphatic system holds key to relieving brain pressure

The glymphatic system was first described by Nedergaard’s lab in 2012 as the brain’s unique waste removal process. Since then, a growing understanding of the mechanics of the system–aided by advanced imaging technologies and AI-driven models of fluid dynamics—has allowed researchers to better predict and manipulate the movement of cerebrospinal fluid (CSF) in the central nervous system.  This research has opened new possibilities to treat Alzheimer’s and other neurological disorders and more effectively deliver and distribute drugs in the central and peripheral nervous system, including the inner ear.  

The new study points to the potential to repurpose the glymphatic system to act as an emergency pressure release valve.  Cerebral edema is a common consequence of moderate and severe cases of TBI.  “In other parts of the body, edema helps with tissue repair, but because of the skull, the brain has limited capacity for expansion.  As a result, pressure increases, blood supply decreases, and debris and toxic proteins are trapped at the injury site, compounding the damage and impairing recovery,” said Rashad Hussain, PhD, an assistant professor in the Center for Translational Neuromedicine and first author of the study.

Trading Sickness for Health: Swapping Brain Cells Points to New Huntington's Therapies

Monday, July 17, 2023

New research appearing in the journal Nature Biotechnology answers important questions about the viability of treatments that seek to replace diseased and aged cells in the central nervous system with healthy ones.  Its findings have implications for a number of neurological and psychiatric disorders—including Huntington’s disease, amyotrophic lateral sclerosis (ALS), and schizophrenia—that have been linked to glia, a population of cells that support brain health and function. 

“A broad variety of disorders we associate with neuronal loss now appear to be caused by dysfunctional glial cells,” said Steve Goldman, MD, PhD, co-director of the Center for Translational Neuromedicine at the University of Rochester lead author of the new study. “This makes these diseases attractive targets for stem and progenitor cell-based therapies.”

The new study describes the ability of human glial progenitor cells–precursor cells that can give rise to both astrocytes and oligodendrocytes, the two major types of glia—to compete with one another in the adult brain, and the competitive advantage of young and healthy cells over aged and diseased cells.

An Unexpected Doorway into the Ear Opens New Possibilities for Hearing Restoration

Wednesday, June 28, 2023

An international team of researchers led by the co-director of the Center for Translational Neuromedicine developed a new method to deliver drugs into the inner ear. It harnesses the natural flow of fluids in the brain and employs a little-understood back door into the cochlea.

Images capture unseen details of the synapse

Wednesday, June 14, 2023

Scientists have created one of the most detailed 3D images of the synapse, the important juncture where neurons communicate with each other through an exchange of chemical signals.  These nanometer scale models will help scientists better understand and study neurodegenerative diseases such as Huntington’s disease and schizophrenia. 

The new study appears in the journal PNAS and was authored by a team led by Steve Goldman, MD, PhD, co-director of the Center for Translational Neuromedicine at the University of Rochester and the University of Copenhagen. The findings represent a significant technical achievement that allows researchers to study the different cells that converge at individual synapses at a level of detail not previously achievable. 

“It is one thing to understand the structure of the synapse from the literature, but it is another to see the precise geometry of interactions between individual cells with your own eyes,” said Abdellatif Benraiss, PhD, a research associate professor in the Center for Translational Neuromedicine and co-author of the study. “The ability to measure these extremely small environments is a young field, and holds the potential to advance our understanding of a number of neurodegenerative and neuropsychiatric diseases in which synaptic function is disturbed.”

Anders Jahre Main Award for Medical Research given to Maiken Nedergaard

Tuesday, June 13, 2023

The professor of Neurology and co-director of the Center for Translational Neuromedicine at the University of Rochester and University of Copenhagen received the award from the University of Oslo. Nedergaard was recognized for her research on astrocytes and the glymphatic system, which "has far-reaching implications both for understanding how the brain normally works and what goes wrong when the brain is affected by disease."

Maiken Nedergaard's lab just discovered a new part of the brain's waste disposal system

Thursday, January 5, 2023

New Scientist, January 5

The new structure is a fourth membrane, lying on top of the innermost membrane, called the subarachnoid lymphatic-like membrane (SLYM). The SLYM hadn’t been noticed before, partly because the membrane disintegrates when the brain is removed from the skull in post-mortems, says Maiken Nedergaard, a professor of neurology and of neurosurgery and codirector of the Center for Translational Neuromedicine, who helped discover the structure. It is also too thin to be seen in living people via brain-scanning machines.