PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Drug shows early promise in treating seizures

2013-11-18
(Press-News.org) Contact information: Mark Michaud
mark_michaud@urmc.rochester.edu
585-273-4790
University of Rochester Medical Center
Drug shows early promise in treating seizures A study out today in the journal Nature Medicine suggests a potential new treatment for the seizures that often plague children with genetic metabolic disorders and individuals undergoing liver failure. The discovery hinges on a new understanding of the complex molecular chain reaction that occurs when the brain is exposed to too much ammonia. The study shows that elevated levels of ammonia in the blood overwhelm the brain’s defenses, ultimately causing nerve cells to become overexcited. The researchers have also discovered that bumetanide – a diuretic drug used to treat high blood pressure – can restore normal electrical activity in the brains of mice with the condition and prevent seizures. "Ammonia is a ubiquitous waste product of regular protein metabolism, but it can accumulate in toxic levels in individuals with metabolic disorders," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article. "It appears that the key to preventing the debilitating neurological effects of ammonia toxicity is to correct a molecular malfunction which causes nerve cells in the brain to become chemically unbalanced." In healthy people, ammonia is processed in the liver, converted to urea, and expelled from the body in urine. Because it is a gas, ammonia can slip through the blood-brain-barrier and make its way into brain tissue. Under normal circumstances, the brain’s housekeeping cells – called astrocytes – sweep up this unwanted ammonia and convert it into a compound called glutamine which can be more easily expelled from the brain. However, individuals with certain genetic metabolic disorders and people with impaired liver function because of chronic hepatitis, alcoholism, acetaminophen overdose, and other toxic liver conditions cannot remove ammonia from their bodies quickly enough. The result is a larger than normal concentration of ammonia in the blood, a condition called hyperammonemia. When too much ammonia makes its way into the central nervous system, it can lead to tremors, seizures and, in extreme cases, can cause comas and even lead to death. In children with metabolic disorders the frequent seizures can lead to long-term neurological impairment. While ammonia has long been assumed to be the culprit behind the neurological problems associated with inherited metabolic disorders and liver failure, the precise mechanisms by which it triggers seizures and comas have not been fully understood. The new study reveals that ammonia causes a chain of events that alters the chemistry and electrical activity of the brain’s nerve cells, causing them to fire in uncontrolled bursts. One of the keys to unraveling the effects of ammonia on the brain has been new imagining technologies such as two-photon microscopy which allow researchers to watch this phenomenon in real time in the living brains of mice. As suspected, they observed that when high levels of ammonia enter the brain, astrocytes become quickly overwhelmed and cannot remove it fast enough. The abundant ammonia in the brain mimics the function of potassium, an important player in neurotransmission, and tricks neurons into becoming depolarized. This makes it more likely that electrical activity in the brain will exceed the threshold necessary to trigger seizures. Furthermore, the researchers observed that one of the neuron’s key molecular gatekeepers – a transporter known as NKCC1 – was also fooled into thinking that the ammonia was potassium. As a result, it went into overdrive, loading neurons with too much chloride. This in turn prevents the cells from stabilizing itself after spikes in activity, keeping the cells in a heightened level of electrical "excitability." The team found that the drug bumetanide, a known NKCC1 inhibitor, blocked this process and prevented the cells from overloading with chloride. By knocking down this "secondary" cellular effect of ammonia, the researchers were able to control the seizures in the mice and prolong their survival. "The neurologic impact of hyperammonemia is a tremendous clinical problem without an effective medical solution," said Nedergaard. "The fact that bumetanide is already approved for use gives us a tremendous head start in terms of developing a potential treatment for this condition. This study provides a framework to further explore the therapeutic potential of this and other NKCC1 inhibitors." ### Additional co-authors include Fushun Wang, Maria Cotrina, Michel Chen, and Ning Kang with URMC, Vinita Rangroo Thrane, Alexander Thrane and Erlend Nagelhus with the University of Oslo in Norway, and Nathan Smith with the University of Utah. The study was supported with funding from the National Institutes of Health, the Research Council of Norway, the Nordic Center of Excellence Program, the Letten Foundation, and the Fulbright Foundation. END


ELSE PRESS RELEASES FROM THIS DATE:

Scientists invent self-healing battery electrode

2013-11-18
Scientists invent self-healing battery electrode Researchers have made the first battery electrode that heals itself, opening a new and potentially commercially viable path for making the next generation of lithium ion batteries for electric ...

Researchers identify main genes responsible for asthma attacks in children

2013-11-18
Researchers identify main genes responsible for asthma attacks in children An international team spearheaded by researchers from the University of Copenhagen has identified the genes that put some children at particularly high risk of serious asthma attacks, ...

2 for 1 in solar power

2013-11-18
2 for 1 in solar power Solar cells offer the opportunity to harvest abundant, renewable energy. Although the highest energy light occurs in the ultraviolet and visible spectrum, most solar energy is in the infrared. There is a trade-off in harvesting this light, ...

Oxygen, phosphorous and early life on Earth

2013-11-18
Oxygen, phosphorous and early life on Earth Two billion years ago the Earth system was recovering from perhaps the single-most profound modification of its surface environments: the oxygenation of the atmosphere and oceans. This led ...

Study compares outcomes of device for chest compressions vs manual CPR

2013-11-18
Study compares outcomes of device for chest compressions vs manual CPR Chicago – Sten Rubertsson, M.D., Ph.D., of Uppsala University, Sweden and colleagues assessed whether cardiopulmonary resuscitation (CPR) in which chest compressions are delivered ...

Effect of lowering of body temperature for adults with cardiac arrest prior to hospital arrival

2013-11-18
Effect of lowering of body temperature for adults with cardiac arrest prior to hospital arrival Chicago – Francis Kim, M.D., of Harborview Medical Center, Seattle, and colleagues evaluated whether early prehospital cooling (lowering body temperature) improved survival ...

Effect of reducing blood pressure with medications immediately following ischemic stroke

2013-11-18
Effect of reducing blood pressure with medications immediately following ischemic stroke Chicago – Jiang He, M.D., Ph.D., of the Tulane University School of Public Health and Tropical Medicine, New Orleans, and colleagues examined whether moderate lowering of blood ...

Human error most common cause of birth asphyxia

2013-11-18
Human error most common cause of birth asphyxia Compensation claims cite poor fetal monitoring in 50 percent of cases Findings from a 15-year study published in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, ...

Influence of pro-smoking media messages lasts 7 days, study finds

2013-11-18
Influence of pro-smoking media messages lasts 7 days, study finds Exposure to a single pro-smoking media message increases college-aged students' risk of using tobacco for seven days, providing new clues about the influence of media on smoking, according to a new RAND Corporation ...

Ancient, modern DNA tell story of first humans in the Americas

2013-11-18
Ancient, modern DNA tell story of first humans in the Americas CHAMPAIGN, Ill. — University of Illinois anthropology professor Ripan Malhi looks to DNA to tell the story of how ancient humans first came to the Americas and what happened to them once ...

LAST 30 PRESS RELEASES:

Thirty-year mystery of dissonance in the “ringing” of black holes explained

Less intensive works best for agricultural soil

Arctic rivers project receives “national champion” designation from frontiers foundation

Computational biology paves the way for new ALS tests

Study offers new hope for babies born with opioid withdrawal syndrome

UT, Volkswagen Group of America celebrate research partnership

New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll

Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes

University of Cincinnati Cancer Center presents research at AACR 2025

Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025

AACR: Researchers share promising results from MD Anderson clinical trials

New research explains why our waistlines expand in middle age

Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker

Chips off the old block

Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia

Cutting the complexity from digital carpentry

Lung immune cell type “quietly” controls inflammation in COVID-19

Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity

State and sociodemographic trends in US cigarette smoking with future projections

Young adults drive historic decline in smoking

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Chimpanzee stem cells offer new insights into early embryonic development

This injected protein-like polymer helps tissues heal after a heart attack

FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology

In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity

Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects

A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate

Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative

Structure dictates effectiveness, safety in nanomedicine

[Press-News.org] Drug shows early promise in treating seizures