Study raises questions about use of anti-epilepsy drugs in newborns
A brain study in infant rats demonstrates that the anti-epilepsy drug phenobarbital stunts neuronal growth, which could prompt new questions about using the first-line drug to treat epilepsy in human newborns.
In Annals of Neurology EarlyView posted online May 11, researchers at Georgetown University Medical Center (GUMC) report that the anti-epilepsy drug phenobarbital given to rat pups about a week old changed the way the animals' brains were wired, causing cognitive abnormalities later in life.
The researchers say it has been known that some of the drugs used to treat epilepsy increase the amount of neurons that die shortly after birth in the rat brain, but, until this study, no one had shown whether this action had any adverse impact on subsequent brain development.
"Our study is the first to show that the exposure to these drugs -- and just a single exposure -- can prevent brain circuits from developing their normal connectivity, meaning they may not be wired correctly, which can have long-lasting effects on brain function," says the study's senior investigator, Karen Gale, Ph.D., a professor of pharmacology at GUMC. "These findings suggest that in the growing brain, these drugs are not as benign as one would like to believe."
For their study, the Georgetown researchers studied four agents including phenobarbital.
"The good news is not all anti-epilepsy drugs have this disruptive effect in the animal studies," Gale says.
The researchers found that the anti-epilepsy drug levetiracetam did not stunt synaptic growth. Animals treated with a third drug, lamotrigine, showed neural maturation, but it was delayed. An additional finding involved melatonin. When added to phenobarbital, it appeared to prevent the persistent adverse neural effects in the rat pups. Melatonin has been used clinically to protect cells from injury in humans.
"Many clinicians have been advocating for a reexamination of the use of these drugs in infants, and our findings provide experimental data to support that need," says the study's co-lead investigator, Patrick A. Forcelli, Ph.D., a postdoctoral fellow in the department of pharmacology and physiology at GUMC. "Phenobarbital has been used to treat seizures for over 100 years -- well before a Food and Drug Administration approval process was established-- and for more than 50 years, it has been the first drug of choice in the treatment of seizures in neonates."
According to the Epilepsy Foundation, epilepsy affects more than 300,000 Americans under the age of 15. Seizures in neonates are relatively common, and seizure incidence peaks in the first year of life and remains at a high level up to age four.
Recent studies of IQ and other measurements of cognitive function in children have suggested that exposure to certain anti-epilepsy drugs, either in utero or infancy, affects brain function, but the issue is highly controversial, Forcelli says.
"Seizures do not happen to a normal healthy brain," he says. "They are typically associated with, or are a result of, an injury or another neurological condition. So the issue is: what causes later deficits in function -- the underlying condition, the seizures, or the drug used to treat the seizures or some combination of these? Our study in otherwise normal animals suggests that drugs by themselves can be a significant factor."
The Georgetown researchers say their study was designed to look directly at the effect of the different drugs on normal growth of brain neural networks in otherwise normal animals.
This kind of study can only with research in animals, in which each component (condition, seizure and drug) can be controlled and examined separately and in combination.
This kind of study can only be performed in animal models, in which the drug effects can be examined separately from the effects of either seizures or other complications.
"We were looking for the link between acute drug actions seen in a week-old rat pup and the long-term behavioral deficits we and others have seen in rats and humans," Forcelli says.
The researchers measured communication between neurons in an area of the brain known to be sensitive to anti-epilepsy drugs in baby rats that were 10, 14, or 18 days old. In normal, untreated rats, there was a dramatic increase in communication between neurons in this area during this eight-day period. But this maturation of neurons in the critical brain circuit was not seen in rats that had been treated a week earlier with a single therapeutic dose of phenobarbital or a different drug, phenytoin.
The researchers also tested the effect of the drugs after the pups reached early childhood, and found that those treated with phenobarbital were slow to learn.
"This is an important bridge between molecules and behavior that helps us to understand how early life drug exposure can permanently alter behavioral function in later life of the rats," Forcelli says.
The research group is now planning to find out how the drugs affect brain development in infant animals that also have seizures.
Journal reference: Annals of Neurology
Provided by Georgetown University Medical Center
- Treatment for epilepsy is a possible culprit for development of schizophrenia Oct 20, 2009 | not rated yet | 0
- Could drugs for mood disorders, pain and epilepsy cause psychiatric disorders later in life? Oct 20, 2009 | not rated yet | 0
- Dodging the cognitive hit of early-life seizures Dec 13, 2011 | not rated yet | 0
- Early treatment stops epilepsy in its tracks Dec 13, 2007 | not rated yet | 0
- New medication offers hope to patients with frequent, uncontrollable seizures Apr 18, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization ...
Neuroscience 18 hours ago | 4 / 5 (4) | 0
How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.
Neuroscience 18 hours ago | 4 / 5 (2) | 2
One of the major frontiers of modern science is a comprehensive understanding of the human brain and its functions to guide the development of new technologies in information and communication. In a major announcement for ...
Neuroscience 19 hours ago | 3.7 / 5 (3) | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
Neuroscience May 23, 2013 | 4.9 / 5 (9) | 0 |
(Medical Xpress)—The human brain is able to identify individuals' voices by comparing them against an internal 'average voice' prototype, according to neuroscientists.
Neuroscience May 23, 2013 | 3.7 / 5 (3) | 3 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
19 hours ago | 5 / 5 (3) | 0 |
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
13 hours ago | 3 / 5 (2) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
16 hours ago | 3.7 / 5 (3) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
16 hours ago | 5 / 5 (4) | 0 |
(Medical Xpress)—The way Alzheimer's disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics professor.
20 hours ago | not rated yet | 2
(Medical Xpress)—Patients with diabetes who are depressed are much more likely to develop episodes of dangerously low blood sugars, or hypoglycemia, than are those who are not depressed, a new study has ...
20 hours ago | not rated yet | 0 |