Featured Research

from universities, journals, and other organizations

Neuroscientists' discovery could bring relief to epilepsy sufferers; Computational model of epileptic seizures at molecular level

Date:
July 1, 2011
Source:
University of California - Riverside
Summary:
Researchers have made a discovery that could help drug manufacturers develop new antiepileptic drugs and explore novel strategies for treating seizures associated with epilepsy. The researchers used a computational model of the cortical network to show that during seizure there is a slow and progressive buildup of intracellular sodium in neurons, and that it is this accumulation of intracellular sodium that leads to the termination of the seizure.

Researchers at the University of California, Riverside have made a discovery in the lab that could help drug manufacturers develop new antiepileptic drugs and explore novel strategies for treating seizures associated with epilepsy -- a disease affecting about two million Americans.

Neurons, the basic building blocks of the nervous system, are cells that transmit information by electrical and chemical signaling. During epileptic seizures, which generally last from a few seconds to minutes and terminate spontaneously, the concentrations of ions both inside the neuron and the space outside the neuron change due to abnormal ion flow to and from neurons through ion "channels" -- tiny gateways that are embedded to the surface of the neuron.

Ordinarily, intracellular (inside the cell) sodium concentration is low compared to extracellular sodium (the reverse is true of potassium). During seizure, however, there is a buildup of intracellular sodium, with sodium ions moving into neurons from the extracellular space, and potassium ions doing the opposite.

To understand exactly how neurons function during epileptic seizures, Maxim Bazhenov, an associate professor of cell biology and neuroscience, and Giri P. Krishnan, a postdoctoral researcher in his lab, developed and used realistic computer simulations in their analyses and found that while there is a progressive and slow increase in intracellular sodium during seizure, it is this accumulation of intracellular sodium that leads to the termination of the seizure.

"According to our model, sodium concentration reaches a maximum just before the seizure terminates," Bazhenov said. "After seizure initiation, this intracellular sodium buildup is required to terminate the seizure."

The researchers' computational model simulates the cortical network. (The cortex is the outer layer of the cerebrum of the mammalian brain. A sheet of neural tissue, it is often referred to as gray matter.) The model simulates neurons, connections between neurons, variable extracellular and intracellular concentrations for sodium and potassium ions and variable intracellular concentrations for chloride and calcium ions.

Bazhenov explained that conventional antiepileptic drugs are commonly designed to target various sodium channels in order to reduce their activity.

"These drugs essentially slow down the intracellular build-up of sodium, but this only prolongs seizure duration," he said. "This is because seizure duration is affected by the rate of intracellular sodium accumulation -- the slower this rate, the longer the seizure duration."

According to Bazhenov, targeting the sodium channels is not the best approach for drugs to take. He explained that even for drugs to increase the activity of the sodium channels (in order to reduce seizure duration) there is an undesirable effect: seizures become more likely.

"The drugs ought to be targeting other ion channels, such as those responsible for the buildup of intracellular chloride," he advises. "According to our model, restricting the chloride increase would lead to a faster termination of seizure and can even make seizures impossible."

Bazhenov and Krishnan's model also shows that the occurrence of seizures depends critically on the activity of ionic "pumps" -- structures that are also embedded to the surface of neurons. These pumps help remove the sodium and chloride ions from inside the neurons and critically influence their concentrations in the brain.

Study results appear in the June 15 issue of The Journal of Neuroscience.

The research was supported by a grant to Bazhenov from the National Institutes of Health.

Epilepsy is a chronic neurological condition characterized by recurrent seizures -- involuntary changes in body movement or function, sensation, awareness or behavior. The seizures are caused by abnormally excited electrical signals in the brain. It is estimated that about 10 percent of people will experience a seizure some time during their lifetime; about 3 percent will have had a diagnosis of epilepsy by age 80. Epilepsy cannot be transmitted from person to person. No definite cause for epilepsy has been identified.


Story Source:

The above story is based on materials provided by University of California - Riverside. Note: Materials may be edited for content and length.


Journal Reference:

  1. Giri P. Krishnan, Maxim Bazhenov. Ionic Dynamics Mediate Spontaneous Termination of Seizures and Postictal Depression State. The Journal of Neuroscience, 2011; 31 (24): 8870-8882 DOI: 10.1523/%u200BJNEUROSCI.6200-10.2011

Cite This Page:

University of California - Riverside. "Neuroscientists' discovery could bring relief to epilepsy sufferers; Computational model of epileptic seizures at molecular level." ScienceDaily. ScienceDaily, 1 July 2011. <www.sciencedaily.com/releases/2011/06/110621131330.htm>.
University of California - Riverside. (2011, July 1). Neuroscientists' discovery could bring relief to epilepsy sufferers; Computational model of epileptic seizures at molecular level. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2011/06/110621131330.htm
University of California - Riverside. "Neuroscientists' discovery could bring relief to epilepsy sufferers; Computational model of epileptic seizures at molecular level." ScienceDaily. www.sciencedaily.com/releases/2011/06/110621131330.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins