UCI neuroscientists create fiber-optic method of arresting epileptic seizures

UC Irvine neuroscientists have developed a way to stop epileptic seizures with fiber-optic light signals, heralding a novel opportunity to treat the most severe manifestations of the brain disorder.

Using a mouse model of temporal lobe epilepsy, Ivan Soltesz, Chancellor’s Professor and chair of anatomy & neurobiology, and colleagues created an EEG-based computer system that activates hair-thin optical strands implanted in the brain when it detects a real-time seizure.

These fibers subsequently “turn on” specially expressed, light-sensitive proteins called opsins, which can either stimulate or inhibit specific neurons in select brain regions during seizures, depending on the type of opsin.

The researchers found that this process was able to arrest ongoing electrical seizure activity and reduce the incidence of severe “tonic-clonic” events.

“This approach is useful for understanding how seizures occur and how they can be stopped experimentally,” Soltesz said. “In addition, clinical efforts that affect a minimum number of cells and only at the time of a seizure may someday overcome many of the side effects and limitations of currently available treatment options.”

Study results appear online in Nature Communications.

More than 3 million Americans suffer from epilepsy, a condition of recurrent spontaneous seizures that occur unpredictably, often cause changes in consciousness, and can preclude normal activities such as driving and working. In at least 40 percent of patients, seizures cannot be controlled with existing drugs, and even in those whose seizures are well controlled, the treatments can have major cognitive side effects.

Although the study was carried out in mice, not humans, Soltesz said the work could lead to a better alternative to the currently available electrical stimulation devices.

Mild brain cooling after head injury prevents epileptic seizures in lab study

Mild cooling of the brain after a head injury prevents the later development of epileptic seizures, according to an animal study reported this month in the Annals of Neurology.

Epilepsy can result from genetics or brain damage. Traumatic head injury is the leading cause of acquired epilepsy in young adults. It is often difficult to manage with antiepileptic drugs. The mechanisms  behind the onset of epileptic seizures after brain injury are not known . There is currently no treatment to cure it, prevent it, or even limit its severity.

The multi-institutional research team used a rodent model of acquired epilepsy in which animals develop chronic spontaneous recurrent seizures -the hallmark of epilepsy- after a contusive head injury similar to that causing epilepsy in humans. The rats were randomized to either mock-cooling or cooling of the contused brain by no more than 2 Celsius degrees. This degree of cooling, the authors explained, is known to be safe and to decrease mortality of patients with head injury.  The rats  were then monitored for four months after injury and epilepsy was evaluated by intracranial EEG. The contused brain was cooled continuously with special headsets engineered to passively dissipate heat. No Peltier cells or other power sources for refrigeration were needed.

The investigators report that cooling by just 2 degrees celsius for 5 weeks beginning 3 days after injury virtually abolished the later development of epileptic seizure activity. This effect persisted through the end of the study. The treatment induced no additional pathology or inflammation, and restored neuronal activity depressed by the injury.

“These findings demonstrate for the first time that prevention of epileptic seizures after traumatic brain brain injury is possible, and that epilepsy prophylaxis in patients could be achieved more easily than previously thought, said  the lead author of the study,  Raimondo D’Ambrosio, UW associate professor of neurological surgery.  He added that a clinical trial is required to verify the findings in head injury patients.

Brake on nerve cell activity after seizures discovered

Given that epilepsy impacts more than 2 million Americans, there is a pressing need for new therapies to prevent this disabling neurological disorder. New findings from the neuroscience laboratory of Mark S. Shapiro, Ph.D., at The University of Texas Health Science Center at San Antonio, published Dec. 20 in the high-impact scientific journal, Neuron, may provide hope.

“A large fraction of epilepsy sufferers cannot take drugs for their disorder or the existing drugs do not manage it,” said Dr. Shapiro, professor of physiology in the School of Medicine. “As a result, many opt for surgery to remove the hippocampus, a part of the brain where memories are stored but also where seizures are often localized. The heart-wrenching choice is between their memories and the epilepsy.”

Genes go into action
A major finding of the study is that selected genes get switched on during and after a seizure, sending swarms of signals to reduce uncontrolled firing of nerve cells. A medication that amplifies this response after a person’s initial seizure could thus prevent recurrent seizures and the onset of devastating epilepsy.

Uncontrolled electrical activity by specialized electricity-producing proteins in the brain called “ion channels” triggers epileptic seizures. One in 10 people have a lifetime risk of suffering a seizure, which can occur for a variety of reasons including traumatic brain injury, stroke or drug overdoses.

A powerful brake
Although not all seizures lead to epilepsy, some trigger changes in the brain that heighten the risk of the disorder. Dr. Shapiro’s research sheds light on why most isolated seizures do not lead to full-blown epilepsy, whereas others do. An ion channel called the “M-channel” acts as a powerful “brake” on hyper-excitability in the brain. Another organizational protein, called AKAP79, acting much like an air-traffic controller, calls in more M channels as part of neuroprotective response machinery.

Pharmacological therapy to enhance M-channel gene expression or AKAP79 function “could jump-start this neuroprotective mechanism to prevent a seizure from turning into epilepsy,” Dr. Shapiro said. “Administering it right after a traumatic brain injury could be very effective.”

It was not known that electrical activity could regulate M-channel genes, Dr. Shapiro said. Nor was it known that the AKAP79 organizer protein, which coordinates many aspects of M-channel function, could turn on their genes in a person’s DNA. By increasing M-channel expression in the brain, uncontrolled electrical firing of nerve cells in the brain is sharply controlled.

Mouse experiments
The Shapiro lab team records electrical currents and performs imaging in living nerve cells to measure M-channel activity. This study included inducing seizures in healthy mice. After a seizure, gene expression of M-channels in the hippocampus increased more than 10-fold within 24 hours, Dr. Shapiro said. This protective effect was completely absent in mice lacking the mouse version of the AKAP79 gene.

“Because excessive firing of nerve cells is also involved in chronic pains, such as migraines, mood disorders and hypertension, increasing M-channel signals to reduce nerve-cell firing could also likely be effective in treating those conditions,” Dr. Shapiro said.