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There are at least a dozen theories of what is happening in the brain when deep brain stimulation is applied, but the fact is that no one has really understood the process completely, said Robert Bakos, M.D., a neurosurgeon at the University of Rochester and a co-author of the paper, who has performed more than 100 DBS surgeries in the last decade. Weve all been focused on what is happening to the nerve cells in the brain, but it may be that weve been looking at the wrong cell type.

Nedergaards team showed that the electrical pulses that are at the heart of DBS evoke those other cells astrocytes in the area immediately around the surgery to release ATP, which is then broken into adenosine. The extra adenosine reduces abnormal signaling among the brains neurons.

The team also showed that in mice, an infusion of adenosine itself, without any deep brain stimulation, reduced abnormal brain signaling. They also demonstrated that in mice whose adenosine receptors had been blocked, DBS did not work; and they showed that a drug like caffeine that blocks adenosine receptors (the reason why caffeine helps keep us awake) also diminishes the effectiveness of DBS.

It may be possible to enhance the effectiveness of deep brain stimulation by taking advantage of the role of agents that modulate the pathways initiated by adenosine, said Nedergaard. Or, its possible that one could develop another type of procedure, perhaps using local targeting of adenosine pathways in a way that does not involve a surgical procedure.

The latest work continues Nedergaards line of research showing that brain cells other than neurons play a role in a host of human diseases. ATP in the brain is produced mainly by astrocytes, which are much more plentiful in the brain th
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