Researchers from North Carolina State University have mapped the areas of the cerebral cortex implicated in absence epilepsy in mice. What is more, the researchers have shown how transplanting embryonic neural cells into these affected areas can reduce seizure activity, leading to hope of new treatments for humans with absence epilepsy.
Primarily affecting children, absence epilepsy differs from other forms of epilepsy in that it does not cause "clonic-tonic" muscle spasm seizures. Instead, affected patients will "zone out" and stare into space for a short period, often with no memory of the event afterward.
Absence epilepsy is a complex condition and only about one third of patients respond to medication.
A mouse study in 2011, conducted by researchers at the Stanford University School of Medicine in California, identified a circuit in the brain that triggers absence seizures.
This demonstrated for the first time how signaling between the cerebral cortex and the thalamus produced the brief loss of consciousness and unique 33-times-per-second brain oscillations that characterize the absence seizure.
'Hyperactivity' associated with seizures in vision and touch areas of the mouse brain
In the new study, the researchers analyzed the brains of mice bred to have absence epilepsy. They found a link between absence seizures and hyperactivity in the regions of the brain associated with vision and touch.
A mouse looks upward at a transplanted GABAergic neuron (green) in its primary visual cortex.
Image credit: Alice Harvey
These regions are known as the primary visual and primary somatosensory cortices in the occipital and parietal lobes.
Other recent research has shown that inhibitory neurons secreting the gamma-aminobutyric acid (GABA) neurotransmitter are defective in mice with absence seizures. Therefore, the "GABAergic" neurons in the visual and somatosensory cortical areas were likely to be part of the problem, the team surmised.
The researchers then harvested neural stem cells from normal mouse embryos, which were transplanted into the occipital cortexes in a group of absence seizure mice.
Following transplantation, the researchers witnessed dramatic changes in these mice. Absence seizures decreased sharply, the mice gained more weight and they also survived longer than mice who did not receive the transplant.
"This is a profound and remarkably effective first result," says North Carolina State University neurobiology professor Troy Ghashghaei, "and adds to the recent body of evidence that these transplantation treatments can work in mouse models of epilepsy."
However, Prof. Ghashghaei admits that the team still do not understand the mechanisms behind what the normal inhibitory cells are doing in areas of the visual cortex of absence epileptic mice.
"We know that you can get positive results even when a small number of transplanted neurons actually integrate into the cortex of affected mice, which is very interesting. But we don't know how the transplanted cells are connecting with other cells in the cortex and how they alleviate the absence seizures in the mouse model we employed."
Next, Prof. Ghashghaei and colleagues plan to investigate "reprogramming" transplanted cells to to generate GABAergic and other types of neurons. Multiple laboratories around the world are currently devising methods to do just this. The ultimate aim of this work would be to develop new therapies for humans with epilepsy who do not respond to drug treatments.