Harnessing cortical plasticity could prevent stroke damage
MedWire News: Stimulation of a single whisker completely prevents stroke damage in rats with permanent occlusion of the middle cerebral artery (MCA), report US researchers.
There was a tight window for success, however, with complete protection only obtained if whisker stimulation was applied within an hour of MCA occlusion.
Lead researcher Ron Frostig (University of California, Irvine) told MedWire News that the startling findings were actually borne of a failed experiment.
"We were interested in cortical plasticity in adult rats following stroke," he said. "Surprisingly, we failed to create the desired stroke following MCA occlusion, and we decided to understand why."
Whisker stimulation consisted of a single whisker, ipsilateral to the MCA occlusion, being deflected by 9 degrees at a rate of 5 Hz for 1 second. This was repeated at intervals over 2 hours to a cumulative stimulation time of 4.27 minutes. The team previously showed that stimulating a whisker in a rat activates a large cortical area, of about 63 mm3.
If whisker stimulation was started up to 1 hour after permanent MCA occlusion, cortical activation in response to whisker stimulation 24 hours later was similar to that seen before occlusion, and there was no sign of infarction. But in the absence of stimulation, cortical response was lost and the rats sustained infarcts averaging 28.4 mm3.
When whisker stimulation was started from 2 hours after occlusion, six of eight rats were completely protected from stroke damage, but two sustained infarction and had diminished cortical activation in response to whisker stimulation. If whisker stimulation was delayed until 3 hours after occlusion, damage appeared greater than that seen in rats that did not receive any stimulation.
The protective effects of whisker stimulation appeared to be down to reorganization of blood flow, the researchers report in the journal PLoS ONE.
They show that occluding the distal ends of the MCA branches abolished the protective effect of whisker stimulation. Direct visualization of blood flow revealed a marked reduction immediately after MCA occlusion, which persisted to 24 hours in rats given whisker stimulation from 3 hours after occlusion. In contrast, if rats were stimulated immediately after occlusion, blood flow at 24 hours was similar to that before occlusion.
The protective effect of whisker stimulation lasted for at least 7 days, with rats given stimulation exhibiting normal sensorimotor-related behavior at this time point, similar to rats that had undergone sham MCA occlusion.
Frostig hopes to conduct longer-term follow-up, to see how long the effect lasts, but said he believes that the redirected blood flow is "the brain's permanent solution to a permanent ischemia."
He also pointed out that, if the findings prove applicable to humans (stimulating fingertips or lips could have a similar effect), the technique "may have several important advantages over thrombolysis."
As well as potentially avoiding side effects such as intracerebral hemorrhage, it could increase the proportion of patients treated, he said.
"Since our sensory-based protection is not dependent on any drugs and is totally non-invasive, it could, in theory, be applied for victims everywhere, long before they reach the emergency room and therefore it suggests a potential for a better chance to save lives."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Eleanor McDermid