You already associate Ambien with defeating insomnia, writing uncomfortably vivid emails to second-string friends and unknowingly noshing on mustard and ice cream in the middle of the night. Now, a new study, published in the journal Brain, suggests America’s favorite sleep aid could hasten stroke recovery.
Researchers at the Stanford University School of Medicine, according to a press release, found that mice who receive low doses of Zolpidem (generic for Ambien) rebound faster after having strokes than mice who don’t get the goods.
Strokes, which affect 800,000 Americans annually, is the nation’s leading cause of neurologic disability. They’re caused by a lack of blood to the brain, which results either in insufficient flow or brain bleeding, respectively called ischemic and hemorrhagic strokes.
Depending on the type of stroke, resulting damage includes loss of movement, sensation and vision on one side of the body, loss of speech and vertigo. The lost function surfaces quickly, typically within a few hours of an attack. Although drugs and mechanical devices to correct the blockage do exist, they’re only effective if administered within a few hours. With this short timeframe, less than 10 percent of stroke victims, according to the press release, benefit from available therapies.
Most stroke recovery takes place within the subsequent three-to-six months, when the brain repairs damaged tissue, essentially rewiring fried neural connections. As of now, drug therapy hasn’t proven effective in expediting this recovery period. Physical therapy has shown limited success. For the most part, bouncing back from a stroke remains largely a natural process.
The Stanford team wanted to see if low doses of Zolpidem would help stroked mice recover faster by increasing GABA signaling (more on that later). Interestingly enough, earlier research (from a different team) has shown more GABA signaling to interfere with stroke recovery — exactly the opposite of what researchers hoped to see. But, they had a reason to see their hypothesis out, because there are two different kinds of GABA signaling — synaptic and extrasynaptic. The first study looked at extrasynaptic signaling, but the researchers planned to go synaptic and hope for the best.
A Neuro Refresher
Nerve cells signal back and forth by secreting neurotransmitters, including the calming (and earliest-discovered) GABA, receptors for which are littered throughout the brain. After a nerve cell secretes a neurotransmitter, it binds to receptors on the surface of adjacent nerve cells. Zolpidem, like Xanax and a number of sleep drugs, induces drowsiness by binding to GABA receptors. Most signaling takes place in the junction between nerve cells called synapses. And Zolpidem, following the herd, has an affinity for synaptic GABA. A few GABA receptors are located outside the synapse — these extrasynaptic receptors were the focus of the 2010 research linking delayed stroke recovery with GABA signaling.
Researchers suspected post-stroke benefits from GABA signaling for good reason: They observed temporary increase in synaptic activity near a stroke-damaged brain region (in mice) known to rewire itself during recovery. The GABA signaling uptick peaked shortly after recovery, before returning to normal levels within a month’s time. And the signaling fluctuations only happened in a part of the cerebral cortex that dispatches messages to the spinal cord, a brain process important to motor control.
So, they were able to link a fleeting increase in GABA signaling with brain tissue recovery.
But they didn’t know whether the increase was a good thing or not. In other words, would mice with amped-up synaptic signaling regain lost function at a faster-than-normal rate?
To figure it out, they looped in Ambien.
Researchers artificially gave mice either ischemic or hemorrhagic strokes, which leave different types of damage. Ischemic patients lose sensory function, whereas hemorrhagic patients lose motor function. Then, they put some of the mice on the hypnotic sleep drug. They waited three days so that initial stroke damage was done, and any observed benefits concerned recovery of destroyed tissue, rather than prevention of it.
Additionally, researchers only administered sub-sedation doses of Zolpidem because they couldn’t measure motor coordination in passed-out mice. To demonstrate their dexterous motor skills, mice had to remove tape from their paws (which healthy mice typically do quickly), as well as make their way across a rotating beam.
Because, as mentioned above, Zolpidem goes for synaptic GABA over its homelier extrasynaptic friend, the low doses were likely to affect synaptic signaling only. Across the board, mice-on-meds recovered much faster than chemically deprived rodents — successful tape-removal, for example, took a few days versus a month.
It’s not clear that Zolpidem would have such a substantial effect on stroke recovery in humans because mice, unlike us, naturally reclaim most of their pre-stroke abilities. So, rather than rush into clinical trials, the Stanford team first wants to test Ambien therapy in other stroked subjects, as well as tinker with both the dose and timing of drug administration. Merry Christmas, ya filthy animals.