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Rodent of the Week: Opiate protects against stroke damage

June 19, 2009 |  3:35 pm

Rodent_of_the_week Neuroscientists have long hunted for some simple means of protecting the brain from the ravages of injury caused by stroke, trauma or disease -- either before the insult occurs, or before the die-off of brain cells begins. They've tried lots of odd remedies, including marijuana, magnesium sulfate, mifepristone (the latter two used in staving off premature labor and inducing abortion, respectively). Now, researchers are exploring whether cooling a patient's brain immediately after a stroke or brain injury might reduce long-term damage and disability.

It's a line of inquiry littered with failures. They're often intriguing or instructive failures. But the Holy Grail of "neuroprotection" seems as elusive as ever.

So with tempered hope, we report that drug-induced hibernation appears to be a most effective way to stem the ill effects of stroke -- if you're a rat (with a good drug connection).

(By the way, this is as good a time as any to ask: Do you recognize the signs of stroke?)

These results come from an article published this month in BioMed Central, in which a team led by a researcher from the National Institute on Drug Abuse infused adult Sprague Dawley rats with a "delta opioid peptide" known by the acronym DADLE.

Make no mistake, DADLE is an opiate drug. It puts rodents in a sort of drug-induced state of hibernation. But it happens also to activate a complex repair mechanism in the brain's striatal and cortical areas. And it's an especially ardent rescuer of endangered dopamine neurons, which, when damaged, seem to cause all kinds of disability in rodents and in humans.

The researchers started to infuse the rats with DADLE seven hours before inducing strokes, and, starting a day later, compared the rats pretreated with the hibernation elixir to those infused with a saline solution.

The differences between the two groups were dramatic. On tests of their motor and mental function and in scans showing the health of brain cells, the rats that got saline solution looked like they'd suffered a major stroke; they had massive cell die-offs and substantial mental and motor disability. But the DADLE-treated rats looked and acted virtually as if nothing had happened, both 24 hours and 72 hours after their strokes.

OK, so you're thinking, "How's this going to help me?" First off, humans aren't rats; second, humans don't hibernate; third, it'll do me no good to get hooked on opiates just to limit the damage of a possible stroke; and fourth, few of us are lucky enough to see a stroke coming early enough to dose ourselves ahead of time with a delta opioid peptide like DADLE.

But the DADLE experiment may still help put you back on your feet after a future stroke. Researchers can see which brain regions and which types of brain cells DADLE acts on, and now they've seen how beneficial it can be to tweak those regions and cells to lessen the effect of a stroke. In the bid to find or develop future drugs and therapies, knowing which targets to shoot for will prove valuable, the authors write.

-- Melissa Healy  

Photo: Advanced Cell Technology, Inc.

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