Thursday, December 17, 2009

RESEARCH SHEDS NEW LIGHT ON EPILEPSY

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Scientists at Newcastle University have for the first time been able to record spontaneous epileptic activity in brain tissue that has been removed from patients undergoing neurosurgery.

Led by Newcastle University’s Dr Mark Cunningham, the research has revealed that a particular type of brain wave pattern associated with epilepsy is caused by electrical connections between nerve cells in the brain – rather than chemical ones. This means the traditional drugs are useless to them.

Published in the Proceedings of the National Academy of Sciences (PNAS), Dr Cunningham said the findings marked a huge step forward in our understanding of a disease which affects an estimated 45 million people worldwide.

“Until now we have only been able to mimic epilepsy using experimental animal models but this can never give you a true picture of what is actually going on inside the human brain in epilepsy,” explained Dr Cunningham who is based in Newcastle University’s Institute of Neuroscience.

“Our findings help us to understand what is going wrong and are an important step towards finding new epilepsy treatments in the future.”

The first line of treatment for patients with epilepsy uses anti-epileptic drugs to control seizures.

However, in almost 30 per cent of patients the drugs don’t work. In this case, one course of action available to them is a neurosurgical procedure in which the brain tissue responsible for the epilepsy is removed from the patient.

Working in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital and IBM Watson Research Centre in New York, the team – with permission from the patients – have taken this epileptic tissue into the lab and ‘fooled’ it into thinking it is still part of the living brain.

Supported by experts in the University's School of Computing Science, Dr Cunningham and the team have then been able to record electrical signals from individual neurons and also networks of neurons.

Comparing this with normal brain tissue activity they managed to record an underlying ‘noise’ – a particular type of brain wave, or oscillation, which occurs in the intact epileptic human brain and which scientists believe is a precursor to an epileptic seizure.

Using a combination of experimental techniques, the team have shown that rather than being controlled by chemical signals which most conventional anti-epileptic drugs target, this oscillation relies on direct electrical connections.

“This may explain why the traditional drugs that target chemical connections don’t work for patients with this kind of epilepsy,” explains Dr Cunningham, who conducted the research with his colleague Professor Miles Whittington.

“These findings have massively increased our understanding of epilepsy and offer real hope in terms of finding new ways of tackling the disease.

“The next step is to understand what it is that triggers the transition between the underlying epileptic state of the brain cells and the fast oscillations that are responsible for causing a seizure.”

(Photo: Newcastle U.)

Newcastle University

CPR IS SUCCESSFUL WITHOUT MOUTH-TO-MOUTH, BUT NOT WITHOUT OXYGEN

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People can survive cardiac arrest if they receive only chest compressions during attempts to revive them – as advised by the current American Heart Association guidelines. But they cannot survive without access to oxygen sometime during the resuscitation effort, research suggests.

Scientists tested different scenarios in an animal study of cardiac arrest. Rats received either 100 percent oxygen, 21 percent oxygen – the equivalent of room air – or no oxygen (100 percent nitrogen) at the same time they received cardiopulmonary resuscitation (CPR).

About 80 percent of the rats survived regardless of the percentage of oxygen they received along with chest compressions. However, in the group receiving no oxygen, only one animal could be resuscitated.

Though these animals received the oxygen via ventilation, people who suffer cardiac arrest in a public setting would more likely obtain some oxygen by gasping during CPR or by receiving some air from a vacuum effect resulting from chest compressions, researchers say.

“The study showed that there is a need for oxygen. How much oxygen is needed remains unknown. There is probably a sweet spot in there somewhere,” said Mark Angelos, professor of emergency medicine at Ohio State University and senior author of the study.

“For the first few minutes, it’s probably right just to push on the chest. But at some point you probably need to add oxygen, however you can – maybe mouth-to-mouth or with supplemental oxygen. Where that sweet spot is is not yet clear.”

The research is published in a recent issue of the journal Resuscitation.

According to the American Heart Association, almost 80 percent of cardiac arrests that take place outside a hospital occur at home and are witnessed by a family member. Yet only 6.4 percent of sudden cardiac arrest victims survive because most witnesses do not know how to perform CPR.

The association is in the midst of a new campaign touting “hands-only” CPR, urging people to call 911 and push “hard and fast” in the center of the chest of a person in cardiac arrest.

Angelos said his research is not intended to counter the current guidelines. Instead, scientists continue to study the intricacies of the resuscitation process in the pursuit of ways to improve the potential for survival after cardiac arrest.

Approximately 30 percent of cardiac arrest patients will survive long enough to be hospitalized. But far fewer are ever discharged from the hospital; most typically die of heart failure or brain damage resulting from an extended loss of oxygen to the brain, said Angelos, also an investigator in Ohio State’s Davis Heart and Lung Research Institute.

In the study, Angelos and colleagues imposed six minutes of cardiac arrest on 33 rats before CPR was started. During CPR, animals were ventilated with either 100 percent oxygen or 21 percent oxygen.

A control group of rats received nitrogen, which eliminated oxygen from their lungs. This scenario allowed for lab comparisons, but was not intended to mimic normal conditions because people would likely have some residual oxygen in their lungs and blood even during cardiac arrest.

CPR was continued until the surviving animals experienced what is called the “return of spontaneous circulation,” when the heart pumped blood on its own. All animals receiving oxygen returned to spontaneous circulation at approximately the same time, between about 90 seconds and two minutes after CPR began.

All surviving animals continued to receive the same levels of oxygen that they had received during CPR for two minutes after their hearts started working, and then they were all transferred to 100 percent oxygen for an hour.

“That’s pretty typical for a hospitalized cardiac arrest victim, to get a high concentration of oxygen early on,” Angelos said.

One rat unexpectedly survived CPR without any oxygen, but died within 72 hours. Among the rats receiving oxygen during CPR, nine of 11 (82 percent) of the rats in the 21-percent oxygen group survived CPR, and 10 of 12 (83 percent) of the rats receiving 100 percent oxygen survived. At the 72-hour mark, those figures had dropped: 77 percent of the room-air rats were still alive, and 80 percent of 100-percent oxygen rats were still living.

Neurological tests showed that five of seven (71 percent) of the room-air rats and three of eight (38 percent) of the rats on 100-percent oxygen during CPR returned to normal brain function at 72 hours. The researchers considered these findings secondary to the initial finding that oxygen was required for success during the initial resuscitation process, Angelos noted.

“In a public setting, presumably we don’t have any options. We see that ventilating with room air is just as good as supplemental oxygen,” he said. “However, we also know now that too little or the absence of any ventilation might be harmful, at least over time, due to the lack of oxygen.”

Generally, Angelos noted, the concern has been too much ventilation, which lessens the effectiveness of CPR.

(Photo: OSU)

The Ohio State University

STUDY SHOWS NEW BRAIN CONNECTIONS FORM RAPIDLY DURING MOTOR LEARNING

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New connections begin to form between brain cells almost immediately as animals learn a new task, according to a study published in Nature. Led by researchers at the University of California, Santa Cruz, the study involved detailed observations of the rewiring processes that take place in the brain during motor learning.

The researchers studied mice as they were trained to reach through a slot to get a seed. They observed rapid growth of structures that form connections (called synapses) between nerve cells in the motor cortex, the brain layer that controls muscle movements.

"We found very quick and robust synapse formation almost immediately, within one hour of the start of training," said Yi Zuo, assistant professor of molecular, cell and developmental biology at UCSC.

Zuo's team observed the formation of structures called "dendritic spines" that grow on pyramidal neurons in the motor cortex. The dendritic spines form synapses with other nerve cells. At those synapses, the pyramidal neurons receive input from other brain regions involved in motor memories and muscle movements. The researchers found that growth of new dendritic spines was followed by selective elimination of pre-existing spines, so that the overall density of spines returned to the original level.

"It's a remodeling process in which the synapses that form during learning become consolidated, while other synapses are lost," Zuo said. "Motor learning makes a permanent mark in the brain. When you learn to ride a bicycle, once the motor memory is formed, you don't forget. The same is true when a mouse learns a new motor skill; the animal learns how to do it and never forgets."

Understanding the basis for such long-lasting memories is an important goal for neuroscientists, with implications for efforts to help patients recover abilities lost due to stroke or other injuries.

"We initiated the motor learning studies to understand the process that takes place after a stroke, when patients have to relearn how to do certain things. We want to find out if there are things we can do to speed up the recovery process," Zuo said.

The lead authors of the Nature paper, Tonghui Xu and Xinzhu Yu, are a postdoctoral researcher and doctoral student, respectively, in Zuo's lab at UCSC. Coauthors include Andrew Perlik, Willie Tobin, and Jonathan Zweig of UCSC and Kelly Tennant and Theresa Jones of the University of Texas, Austin.

The study used mice that had been genetically altered to make a fluorescent protein within certain neurons in the brain. The researchers were then able to use a special microscopy technique (two-photon microscopy) to obtain clear images of those neurons near the surface of the brain. The noninvasive imaging technique enabled them to view changes in individual brain cells of the mice before, during, and after the mice were trained in the seed-reaching task.

"We were able to follow the same synapses over time, which had not been done before in a motor learning study," Zuo said. "We showed that structural changes occur in the brain at a much earlier stage than people had believed."

Results from the study suggested that the newly formed dendritic spines are initially unstable and undergo a prolonged selection process during the course of training before being converted into stable synapses.

When previously trained mice were reintroduced to the reaching task four months later, their skill at the task remained high, and images of their brains did not show increased spine formation. When previously trained mice were taught a new skill, however, they showed enhanced spine formation and elimination similar to that seen during the initial training. Furthermore, spines that had formed during the initial training persisted after the remodeling process that accompanied the learning of a new task.

These findings suggest that different motor behaviors are stored using different sets of synapses in the brain, Zuo said. One of the questions she would like to explore in future studies is how these findings apply to different types of learning.

"In China, where I grew up, we memorize a lot in school. What are the changes that take place in the brain during learning and memorizing, and what are the best ways to consolidate those memories? We don't really know the best way to learn and memorize," she said.

(Photo: Xu et al.)

University of California, Santa Cruz

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